ClinVar Genomic variation as it relates to human health
NM_000147.5(FUCA1):c.433T>C (p.Trp145Arg)
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.
Uncertain significance(4); Benign(1); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000147.5(FUCA1):c.433T>C (p.Trp145Arg)
Variation ID: 296890 Accession: VCV000296890.39
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.11 1: 23865582 (GRCh38) [ NCBI UCSC ] 1: 24192072 (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 Dec 6, 2016 Apr 15, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000147.5:c.433T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000138.2:p.Trp145Arg missense NC_000001.11:g.23865582A>G NC_000001.10:g.24192072A>G NG_013346.1:g.7788T>C - Protein change
- W145R
- Other names
- -
- Canonical SPDI
- NC_000001.11:23865581:A:G
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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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0.00060 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00060
1000 Genomes Project 30x 0.00062
Exome Aggregation Consortium (ExAC) 0.00101
The Genome Aggregation Database (gnomAD), exomes 0.00110
Trans-Omics for Precision Medicine (TOPMed) 0.00123
The Genome Aggregation Database (gnomAD) 0.00126
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00146
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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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FUCA1 | - | - |
GRCh38 GRCh37 |
350 | 430 | |
LOC126805661 | - | - | - | GRCh38 | - | 57 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV000313109.18 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Sep 18, 2023 | RCV000993946.20 | |
Likely benign (1) |
no assertion criteria provided
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Jan 1, 2019 | RCV001251773.3 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 28, 2022 | RCV003977840.1 |
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
Help
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
Help
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
Help
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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Uncertain significance
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Fucosidosis
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000896308.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Fucosidosis
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000356771.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Sep 18, 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: SCV001987395.4
First in ClinVar: Nov 06, 2021 Last updated: Sep 30, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge (less)
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Fucosidosis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000812592.6
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024 |
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Likely benign
(Mar 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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FUCA1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004789222.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Uncertain significance
(Jan 01, 2019)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001147194.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 4
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Likely benign
(Jan 01, 2019)
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no assertion criteria provided
Method: clinical testing
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Intellectual disability
Affected status: yes
Allele origin:
uniparental
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Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV001427515.1
First in ClinVar: Aug 15, 2020 Last updated: Aug 15, 2020 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001548744.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The FUCA1 p.Trp145Arg variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs150062050), ClinVar … (more)
The FUCA1 p.Trp145Arg variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs150062050), ClinVar (classified as a VUS by Illumina Clinical Services, Invitae, and Fulgent Genetics for Fucosidosis), and LOVD 3.0. The variant was identified in control databases in 301 of 282896 chromosomes (2 homozygous) at a frequency of 0.001064 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 224 of 129196 chromosomes (freq: 0.001734), South Asian in 38 of 30616 chromosomes (freq: 0.001241), Other in 6 of 7226 chromosomes (freq: 0.00083), Latino in 19 of 35440 chromosomes (freq: 0.000536), African in 10 of 24970 chromosomes (freq: 0.000401), Ashkenazi Jewish in 2 of 10370 chromosomes (freq: 0.000193) and European (Finnish) in 2 of 25124 chromosomes (freq: 0.00008); it was not observed in the East Asian population. The p.Trp145 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. (less)
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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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Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Text-mined citations for rs150062050 ...
HelpRecord last updated Apr 15, 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.