ClinVar Genomic variation as it relates to human health
NM_001079866.2(BCS1L):c.385G>A (p.Gly129Arg)
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_001079866.2(BCS1L):c.385G>A (p.Gly129Arg)
Variation ID: 381524 Accession: VCV000381524.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 218661470 (GRCh38) [ NCBI UCSC ] 2: 219526193 (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 Mar 8, 2017 Feb 14, 2024 Aug 20, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001079866.2:c.385G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001073335.1:p.Gly129Arg missense NM_001257342.2:c.385G>A NP_001244271.1:p.Gly129Arg missense NM_001257343.2:c.385G>A NP_001244272.1:p.Gly129Arg missense NM_001257344.2:c.385G>A NP_001244273.1:p.Gly129Arg missense NM_001318836.2:c.25G>A NP_001305765.1:p.Gly9Arg missense NM_001320717.2:c.385G>A NP_001307646.1:p.Gly129Arg missense NM_001371443.1:c.385G>A NP_001358372.1:p.Gly129Arg missense NM_001371444.1:c.385G>A NP_001358373.1:p.Gly129Arg missense NM_001371446.1:c.385G>A NP_001358375.1:p.Gly129Arg missense NM_001371447.1:c.385G>A NP_001358376.1:p.Gly129Arg missense NM_001371448.1:c.385G>A NP_001358377.1:p.Gly129Arg missense NM_001371449.1:c.385G>A NP_001358378.1:p.Gly129Arg missense NM_001371450.1:c.385G>A NP_001358379.1:p.Gly129Arg missense NM_001371451.1:c.25G>A NP_001358380.1:p.Gly9Arg missense NM_001371452.1:c.-41-289G>A intron variant NM_001371453.1:c.-92G>A 5 prime UTR NM_001371454.1:c.-92G>A 5 prime UTR NM_001371455.1:c.-92G>A 5 prime UTR NM_001371456.1:c.-92G>A 5 prime UTR NM_001374085.1:c.385G>A NP_001361014.1:p.Gly129Arg missense NM_001374086.1:c.-92G>A 5 prime UTR NM_004328.5:c.385G>A NP_004319.1:p.Gly129Arg missense NR_163955.1:n.1397G>A non-coding transcript variant NC_000002.12:g.218661470G>A NC_000002.11:g.219526193G>A NG_008018.1:g.6815G>A NG_033099.1:g.3071C>T LRG_539:g.6815G>A LRG_539t1:c.385G>A LRG_539p1:p.Gly129Arg - Protein change
- G129R, G9R
- Other names
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- Canonical SPDI
- NC_000002.12:218661469: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.
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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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BCS1L | - | - |
GRCh38 GRCh37 |
484 | 519 |
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
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 (2) |
criteria provided, multiple submitters, no conflicts
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Aug 20, 2023 | RCV000432529.9 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Sep 30, 2019 | RCV001329213.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 22, 2022 | RCV002285017.1 |
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
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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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Likely pathogenic
(Sep 30, 2019)
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criteria provided, single submitter
Method: clinical testing
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Leigh syndrome
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001520588.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. Phenotype is variable including muscle weakness, lactic acidosis, variable neuro-psychiatric manifestations … (more)
This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. Phenotype is variable including muscle weakness, lactic acidosis, variable neuro-psychiatric manifestations and cortical visual dysfunction [PMID 20472482, 22991165] (less)
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Pathogenic
(Aug 20, 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: SCV000520844.7
First in ClinVar: Mar 08, 2017 Last updated: Aug 24, 2023 |
Comment:
Published functional studies demonstrate a damaging effect on oxidative phosphorylation (Tuppen et al., 2010).; Not observed at significant frequency in large population cohorts (gnomAD); In … (more)
Published functional studies demonstrate a damaging effect on oxidative phosphorylation (Tuppen et al., 2010).; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30582773, 20472482, 22991165, 34662929, 35305621, 34374989, 37001142) (less)
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Pathogenic
(Oct 22, 2021)
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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: SCV002228280.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has … (more)
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects BCS1L function (PMID: 20472482). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BCS1L protein function. ClinVar contains an entry for this variant (Variation ID: 381524). This missense change has been observed in individuals with clinical features of mitochondrial complex III deficiency (PMID: 20472482, 22991165). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 129 of the BCS1L protein (p.Gly129Arg). (less)
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Pathogenic
(Sep 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex III deficiency nuclear type 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin
Additional submitter:
CUBI - Core Unit Bioinformatics, Berlin Institute of Health
Accession: SCV002574850.1
First in ClinVar: Sep 24, 2022 Last updated: Sep 24, 2022 |
Clinical Features:
Microcephaly (present) , Cerebellar ataxia (present) , Global developmental delay (present) , Abnormal circulating lipid concentration (present) , Short stature (present) , Elevated circulating acylcarnitine … (more)
Microcephaly (present) , Cerebellar ataxia (present) , Global developmental delay (present) , Abnormal circulating lipid concentration (present) , Short stature (present) , Elevated circulating acylcarnitine concentration (present) (less)
Sex: male
Tissue: Blood
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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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Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation. | Tuppen HA | Molecular genetics and metabolism | 2010 | PMID: 20472482 |
Text-mined citations for rs1057521059 ...
HelpRecord last updated Feb 14, 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.