NM_001079866.2(BCS1L):c.1057G>A (p.Val353Met) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 17, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001851699.5

Allele description [Variation Report for NM_001079866.2(BCS1L):c.1057G>A (p.Val353Met)]

NM_001079866.2(BCS1L):c.1057G>A (p.Val353Met)

Gene:

BCS1L:BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001079866.2(BCS1L):c.1057G>A (p.Val353Met)

HGVS:

NC_000002.12:g.218663183G>A
NG_008018.1:g.8528G>A
NG_033099.1:g.1358C>T
NM_001079866.2:c.1057G>AMANE SELECT
NM_001257342.2:c.1057G>A
NM_001257343.2:c.1057G>A
NM_001257344.2:c.1057G>A
NM_001318836.2:c.697G>A
NM_001320717.2:c.1057G>A
NM_001371443.1:c.1057G>A
NM_001371444.1:c.1057G>A
NM_001371446.1:c.1057G>A
NM_001371447.1:c.1057G>A
NM_001371448.1:c.1057G>A
NM_001371449.1:c.1057G>A
NM_001371450.1:c.1057G>A
NM_001371451.1:c.697G>A
NM_001371452.1:c.556G>A
NM_001371453.1:c.556G>A
NM_001371454.1:c.556G>A
NM_001371455.1:c.556G>A
NM_001371456.1:c.556G>A
NM_001374085.1:c.1057G>A
NM_001374086.1:c.556G>A
NM_004328.5:c.1057G>A
NP_001073335.1:p.Val353Met
NP_001244271.1:p.Val353Met
NP_001244272.1:p.Val353Met
NP_001244273.1:p.Val353Met
NP_001305765.1:p.Val233Met
NP_001307646.1:p.Val353Met
NP_001358372.1:p.Val353Met
NP_001358373.1:p.Val353Met
NP_001358375.1:p.Val353Met
NP_001358376.1:p.Val353Met
NP_001358377.1:p.Val353Met
NP_001358378.1:p.Val353Met
NP_001358379.1:p.Val353Met
NP_001358380.1:p.Val233Met
NP_001358381.1:p.Val186Met
NP_001358382.1:p.Val186Met
NP_001358383.1:p.Val186Met
NP_001358384.1:p.Val186Met
NP_001358385.1:p.Val186Met
NP_001361014.1:p.Val353Met
NP_001361015.1:p.Val186Met
NP_004319.1:p.Val353Met
LRG_539:g.8528G>A
NC_000002.11:g.219527906G>A
NR_163955.1:n.2064G>A
Q9Y276:p.Val353Met

Protein change:

V186M; VAL353MET

Links:

UniProtKB: Q9Y276#VAR_018164; OMIM: 603647.0004; dbSNP: rs121908574

NCBI 1000 Genomes Browser:

rs121908574

Molecular consequence:

NM_001079866.2:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001257342.2:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001257343.2:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001257344.2:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318836.2:c.697G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320717.2:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371443.1:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371444.1:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371446.1:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371447.1:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371448.1:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371449.1:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371450.1:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371451.1:c.697G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371452.1:c.556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371453.1:c.556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371454.1:c.556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371455.1:c.556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001371456.1:c.556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374085.1:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374086.1:c.556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004328.5:c.1057G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_163955.1:n.2064G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002262814	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 17, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11528392, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002262814

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 17, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.

de Lonlay P, Valnot I, Barrientos A, Gorbatyuk M, Tzagoloff A, Taanman JW, Benayoun E, Chrétien D, Kadhom N, Lombès A, de Baulny HO, Niaudet P, Munnich A, Rustin P, Rötig A.

Nat Genet. 2001 Sep;29(1):57-60.

PubMed [citation]

PMID:: 11528392

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002262814.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces valine with methionine at codon 353 of the BCS1L protein (p.Val353Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs121908574, ExAC 0.004%). This variant has been observed in individual(s) with mitochondrial complex III deficiency (PMID: 11528392). ClinVar contains an entry for this variant (Variation ID: 6166). 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. Experimental studies have shown that this variant affects BCS1L protein function (PMID: 11528392). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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