ClinVar Genomic variation as it relates to human health
NM_001079866.2(BCS1L):c.413C>T (p.Thr138Met)
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
-
NM_001079866.2(BCS1L):c.413C>T (p.Thr138Met)
Variation ID: 551829 Accession: VCV000551829.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q35 2: 218661498 (GRCh38) [ NCBI UCSC ] 2: 219526221 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Aug 5, 2018 Feb 14, 2024 Apr 27, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001079866.2:c.413C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001073335.1:p.Thr138Met missense NM_001257342.2:c.413C>T NP_001244271.1:p.Thr138Met missense NM_001257343.2:c.413C>T NP_001244272.1:p.Thr138Met missense NM_001257344.2:c.413C>T NP_001244273.1:p.Thr138Met missense NM_001318836.2:c.53C>T NP_001305765.1:p.Thr18Met missense NM_001320717.2:c.413C>T NP_001307646.1:p.Thr138Met missense NM_001371443.1:c.413C>T NP_001358372.1:p.Thr138Met missense NM_001371444.1:c.413C>T NP_001358373.1:p.Thr138Met missense NM_001371446.1:c.413C>T NP_001358375.1:p.Thr138Met missense NM_001371447.1:c.413C>T NP_001358376.1:p.Thr138Met missense NM_001371448.1:c.413C>T NP_001358377.1:p.Thr138Met missense NM_001371449.1:c.413C>T NP_001358378.1:p.Thr138Met missense NM_001371450.1:c.413C>T NP_001358379.1:p.Thr138Met missense NM_001371451.1:c.53C>T NP_001358380.1:p.Thr18Met missense NM_001371452.1:c.-41-261C>T intron variant NM_001371453.1:c.-64C>T 5 prime UTR NM_001371454.1:c.-64C>T 5 prime UTR NM_001371455.1:c.-64C>T 5 prime UTR NM_001371456.1:c.-64C>T 5 prime UTR NM_001374085.1:c.413C>T NP_001361014.1:p.Thr138Met missense NM_001374086.1:c.-64C>T 5 prime UTR NM_004328.5:c.413C>T NP_004319.1:p.Thr138Met missense NR_163955.1:n.1425C>T non-coding transcript variant NC_000002.12:g.218661498C>T NC_000002.11:g.219526221C>T NG_008018.1:g.6843C>T NG_033099.1:g.3043G>A LRG_539:g.6843C>T LRG_539t1:c.413C>T LRG_539p1:p.Thr138Met - Protein change
- T138M, T18M
- Other names
- -
- Canonical SPDI
- NC_000002.12:218661497:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
- 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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
BCS1L | - | - |
GRCh38 GRCh37 |
484 | 520 |
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. |
---|---|---|---|---|
Uncertain significance (1) |
criteria provided, single submitter
|
May 16, 2017 | RCV000666979.1 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Sep 7, 2022 | RCV001855471.3 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Apr 27, 2023 | RCV002282302.2 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(May 16, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
GRACILE syndrome
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000791360.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
|
|
Uncertain significance
(Apr 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002572176.2
First in ClinVar: Sep 17, 2022 Last updated: Jun 03, 2023 |
Comment:
Variant summary: BCS1L c.413C>T (p.Thr138Met) results in a non-conservative amino acid change located in the BCS1, N-terminal domain of the encoded protein sequence. Three of … (more)
Variant summary: BCS1L c.413C>T (p.Thr138Met) results in a non-conservative amino acid change located in the BCS1, N-terminal domain of the encoded protein sequence. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251480 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.413C>T has been reported in the literature in individuals affected with Renal Tubulopathies or hypotonia/Leigh syndrome (Braun_2016, Loiselet_2021, Hikmat_2021). 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. The following publications have been ascertained in the context of this evaluation (PMID: 26489029, 33511646, 34662929). Two ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
|
|
Uncertain significance
(Sep 07, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002132584.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: 551829). This missense change has been observed in individual(s) with BCS1L-related conditions (PMID: 26489029). This variant is present in population databases (rs775793638, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 138 of the BCS1L protein (p.Thr138Met). (less)
|
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 |
---|---|---|---|---|
Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease. | Hikmat O | Annals of clinical and translational neurology | 2021 | PMID: 34662929 |
Cerebral blood flow and acute episodes of Leigh syndrome in neurometabolic disorders. | Loiselet K | Developmental medicine and child neurology | 2021 | PMID: 33511646 |
Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity. | Braun DA | Kidney international | 2016 | PMID: 26489029 |
Text-mined citations for rs775793638 ...
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.