ClinVar Genomic variation as it relates to human health
NM_001079866.2(BCS1L):c.399del (p.Glu133fs)
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.
Pathogenic(3); Likely pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001079866.2(BCS1L):c.399del (p.Glu133fs)
Variation ID: 631845 Accession: VCV000631845.13
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2q35 2: 218661483 (GRCh38) [ NCBI UCSC ] 2: 219526206 (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 27, 2019 May 7, 2024 Mar 8, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001079866.2:c.399del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001073335.1:p.Glu133fs frameshift NM_001257342.2:c.399del NP_001244271.1:p.Glu133fs frameshift NM_001257343.2:c.399del NP_001244272.1:p.Glu133fs frameshift NM_001257344.2:c.399del NP_001244273.1:p.Glu133fs frameshift NM_001318836.2:c.39del NP_001305765.1:p.Glu13fs frameshift NM_001320717.2:c.399del NP_001307646.1:p.Glu133fs frameshift NM_001371443.1:c.399del NP_001358372.1:p.Glu133fs frameshift NM_001371444.1:c.399del NP_001358373.1:p.Glu133fs frameshift NM_001371446.1:c.399del NP_001358375.1:p.Glu133fs frameshift NM_001371447.1:c.399del NP_001358376.1:p.Glu133fs frameshift NM_001371448.1:c.399del NP_001358377.1:p.Glu133fs frameshift NM_001371449.1:c.399del NP_001358378.1:p.Glu133fs frameshift NM_001371450.1:c.399del NP_001358379.1:p.Glu133fs frameshift NM_001371451.1:c.39del NP_001358380.1:p.Glu13fs frameshift NM_001371452.1:c.-41-275del intron variant NM_001371453.1:c.-78del 5 prime UTR NM_001371454.1:c.-78del 5 prime UTR NM_001371455.1:c.-78del 5 prime UTR NM_001371456.1:c.-78del 5 prime UTR NM_001374085.1:c.399del NP_001361014.1:p.Glu133fs frameshift NM_001374086.1:c.-78del 5 prime UTR NM_004328.4:c.399delA NM_004328.5:c.399del NP_004319.1:p.Glu133fs frameshift NM_004328.5:c.399delA NR_163955.1:n.1411del non-coding transcript variant NC_000002.12:g.218661484del NC_000002.11:g.219526207del NG_008018.1:g.6829del NG_033099.1:g.3058del LRG_539:g.6829del LRG_539t1:c.399del - Protein change
- E13fs, E133fs
- Other names
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- Canonical SPDI
- NC_000002.12:218661482:AA: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.
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- Links
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
Help
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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BCS1L | - | - |
GRCh38 GRCh37 |
484 | 520 |
Conditions - Germline
Condition
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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
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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 (2) |
criteria provided, multiple submitters, no conflicts
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Dec 20, 2023 | RCV000801063.8 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 22, 2017 | RCV000778594.4 | |
Pathogenic (2) |
criteria provided, single submitter
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Mar 8, 2024 | RCV001825516.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 25, 2023 | RCV003472307.1 |
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
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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
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
(Aug 22, 2017)
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criteria provided, single submitter
Method: clinical testing
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BCS1L-Related Disorders
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000914901.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The BCS1L c.399delA (p.Glu133AspfsTer25) variant has been reported in one study and is found in one individual with complex III deficiency in a compound heterozygous … (more)
The BCS1L c.399delA (p.Glu133AspfsTer25) variant has been reported in one study and is found in one individual with complex III deficiency in a compound heterozygous state with a missense variant. The variant was also present in the unaffected mother in a heterozygous state (Tegelberg et al. 2017). Control data are unavailable for the p.Glu133AspfsTer25 variant, which is reported at a frequency of 0.00036 in the European American population of the Exome Sequencing Project. Based on the limited evidence, the p.Glu133AspfsTer25 variant is classified as a variant of unknown significance but suspicious for pathogenicity for BCS1L-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Aug 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Pili torti-deafness syndrome
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004210799.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Apr 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003821650.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000940819.5
First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu133Aspfs*25) in the BCS1L gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Glu133Aspfs*25) in the BCS1L gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BCS1L are known to be pathogenic (PMID: 12215968, 17314340, 19162478, 19508421, 22277166, 25895478). This variant is present in population databases (rs751484879, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BCS1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 631845). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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GRACILE syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005039956.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
Comment:
Variant summary: BCS1L c.399delA (p.Glu133AspfsX25) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BCS1L c.399delA (p.Glu133AspfsX25) 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. The variant allele was found at a frequency of 7.6e-05 in 251496 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in BCS1L causing GRACILE Syndrome (7.6e-05 vs 0.00047), allowing no conclusion about variant significance. c.399delA has been reported in the literature in individuals affected with GRACILE Syndrome. These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 631845). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Dec 15, 2020)
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no assertion criteria provided
Method: clinical testing
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GRACILE syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002076349.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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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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Respiratory chain complex III deficiency due to mutated BCS1L: a novel phenotype with encephalomyopathy, partially phenocopied in a Bcs1l mutant mouse model. | Tegelberg S | Orphanet journal of rare diseases | 2017 | PMID: 28427446 |
Exome sequencing reveals novel BCS1L mutations in siblings with hearing loss and hypotrichosis. | Zhang J | Gene | 2015 | PMID: 25895478 |
BCS1L gene mutation presenting with GRACILE-like syndrome and complex III deficiency. | Lynn AM | Annals of clinical biochemistry | 2012 | PMID: 22277166 |
Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene. | Ramos-Arroyo MA | Clinical genetics | 2009 | PMID: 19508421 |
Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient. | Blázquez A | Neuromuscular disorders : NMD | 2009 | PMID: 19162478 |
Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome. | Hinson JT | The New England journal of medicine | 2007 | PMID: 17314340 |
GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L. | Visapää I | American journal of human genetics | 2002 | PMID: 12215968 |
Text-mined citations for rs751484879 ...
HelpRecord last updated May 12, 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.