ClinVar Genomic variation as it relates to human health
NM_000136.3(FANCC):c.37C>T (p.Gln13Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000136.3(FANCC):c.37C>T (p.Gln13Ter)
Variation ID: 12046 Accession: VCV000012046.59
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q22.32 9: 95249255 (GRCh38) [ NCBI UCSC ] 9: 98011537 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 3, 2013 May 1, 2024 Aug 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000136.3:c.37C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000127.2:p.Gln13Ter nonsense NM_001243743.2:c.37C>T NP_001230672.1:p.Gln13Ter nonsense NM_001243744.2:c.37C>T NP_001230673.1:p.Gln13Ter nonsense NC_000009.12:g.95249255G>A NC_000009.11:g.98011537G>A NG_011707.1:g.73455C>T LRG_497:g.73455C>T LRG_497t1:c.37C>T LRG_497p1:p.Gln13Ter - Protein change
- Q13*
- Other names
- p.Q13*:CAG>TAG
- Canonical SPDI
- NC_000009.12:95249254:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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FANCC | - | - |
GRCh38 GRCh37 |
632 | 1957 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Jul 6, 2021 | RCV000012826.26 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 27, 2023 | RCV000115351.13 | |
Pathogenic (2) |
criteria provided, single submitter
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Aug 24, 2023 | RCV000476519.20 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 12, 2021 | RCV001021181.11 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jul 06, 2021)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group C
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002798734.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(May 21, 2019)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group C
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002022334.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Aug 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000549951.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 12046). This variant is also known … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 12046). This variant is also known as c.292C>T. This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 8103176, 8128956, 9207444, 26740942). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs121917784, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln13*) in the FANCC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). (less)
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Pathogenic
(Feb 15, 2018)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia, complementation group C
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917333.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: FANCC c.37C>T (p.Gln13X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: FANCC c.37C>T (p.Gln13X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.65G>A, p.Trp22X; c.553C>T, p.Arg185X; c.1642C>T, p.Arg548X). The variant allele was found at a frequency of 8.1e-06 in 245648 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in FANCC causing Fanconi Anemia Group C (8.1e-06 vs 1.80E-03), allowing no conclusion about variant significance. c.37C>T has been reported in the literature in multiple individuals affected with Fanconi Anemia Group C (De Rocco_2014, Gillio_1997, Susswein_2015). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group C
Affected status: unknown
Allele origin:
germline
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Baylor Genetics
Accession: SCV001163262.1
First in ClinVar: Feb 28, 2020 Last updated: Feb 28, 2020 |
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Likely pathogenic
(May 27, 2014)
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criteria provided, single submitter
Method: literature only
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Fanconi anemia, complementation group C
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220353.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Apr 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000149260.14
First in ClinVar: May 17, 2014 Last updated: May 06, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in the heterozygous state in individuals with breast and other cancers referred for genetic testing at GeneDx; This variant is associated with the following publications: (PMID: 17384215, 8103176, 8844212, 24584348, 26596371, 12552564, 8128956, 29922827, 26740942, 12670332, 20869034, 12393516, 10666230, 15516848, 9207444, 26681312, 8639804, 31937788, 29625052, 31589614) (less)
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Pathogenic
(Aug 12, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001182762.4
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.Q13* pathogenic mutation (also known as c.37C>T), located in coding exon 1 of the FANCC gene, results from a C to T substitution at … (more)
The p.Q13* pathogenic mutation (also known as c.37C>T), located in coding exon 1 of the FANCC gene, results from a C to T substitution at nucleotide position 37. This changes the amino acid from a glutamine to a stop codon within coding exon 1. This alteration has been reported in the homozygous and compound heterozygous state in multiple individuals with a clinical diagnosis of Fanconi anemia (Verlander PC et al. Am. J. Hum. Genet., 1994 Apr;54:595-601; Murer-Orlando M et al. Lancet, 1993 Sep;342:686; Gillio AP et al. Blood, 1997 Jul;90:105-10; Nicchia E et al. Mol Genet Genomic Med, 2015 Nov;3:500-12). In addition to the information presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Sep 11, 1993)
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no assertion criteria provided
Method: literature only
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FANCONI ANEMIA, COMPLEMENTATION GROUP C
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000033066.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 18, 2015 |
Comment on evidence:
By mismatch analysis with chemical cleavage with osmium tetroxide and hydroxylamine, Murer-Orlando et al. (1993) demonstrated compound heterozygosity for a gln13-to-ter (Q13X) mutation in exon … (more)
By mismatch analysis with chemical cleavage with osmium tetroxide and hydroxylamine, Murer-Orlando et al. (1993) demonstrated compound heterozygosity for a gln13-to-ter (Q13X) mutation in exon 1 of the FACC gene and an R548X mutation in exon 14 (613899.0005) in chorionic villus samples obtained for prenatal diagnosis of Fanconi anemia of complementation group C (FANCC; 227645). The 2 mutations were derived from the father and mother, respectively, and were also demonstrated in an affected sib. Chromosome breakage analysis on cultured chorionic cells had shown a higher response to diepoxybutane in the pregnancy at risk than in normal control samples. (less)
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Pathogenic
(Feb 28, 2020)
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no assertion criteria provided
Method: curation
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Fanconi anemia complementation group C
Affected status: yes
Allele origin:
germline
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Leiden Open Variation Database
Accession: SCV001365306.1
First in ClinVar: Jun 29, 2020 Last updated: Jun 29, 2020 |
Comment:
Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.
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Pathogenic
(Mar 17, 2017)
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no assertion criteria provided
Method: clinical testing
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002081319.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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Fanconi anemia complementation group C
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000057807.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
Comment:
Common in northern Europeans
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Fanconi Anemia. | Adam MP | - | 2021 | PMID: 20301575 |
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
Identification of point mutations and large intragenic deletions in Fanconi anemia using next-generation sequencing technology. | Nicchia E | Molecular genetics & genomic medicine | 2015 | PMID: 26740942 |
Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology. | De Rocco D | Haematologica | 2014 | PMID: 24584348 |
Genetic subtyping of Fanconi anemia by comprehensive mutation screening. | Ameziane N | Human mutation | 2008 | PMID: 17924555 |
Phenotypic consequences of mutations in the Fanconi anemia FAC gene: an International Fanconi Anemia Registry study. | Gillio AP | Blood | 1997 | PMID: 9207444 |
Novel mutations and polymorphisms in the Fanconi anemia group C gene. | Gibson RA | Human mutation | 1996 | PMID: 8844212 |
Mutation analysis of the Fanconi anemia gene FACC. | Verlander PC | American journal of human genetics | 1994 | PMID: 8128956 |
FACC gene mutations and early prenatal diagnosis of Fanconi's anaemia. | Murer-Orlando M | Lancet (London, England) | 1993 | PMID: 8103176 |
Text-mined citations for rs121917784 ...
HelpRecord last updated May 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.