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NM_001079866.2(BCS1L):c.548G>A (p.Arg183His) AND Leigh syndrome

Clinical significance:Pathogenic (Last evaluated: Feb 1, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000779835.1

Allele description [Variation Report for NM_001079866.2(BCS1L):c.548G>A (p.Arg183His)]

NM_001079866.2(BCS1L):c.548G>A (p.Arg183His)

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.548G>A (p.Arg183His)
HGVS:
  • NC_000002.12:g.218661846G>A
  • NG_008018.1:g.7191G>A
  • NG_033099.1:g.2695C>T
  • NM_001079866.2:c.548G>AMANE SELECT
  • NM_001257342.2:c.548G>A
  • NM_001257343.2:c.548G>A
  • NM_001257344.2:c.548G>A
  • NM_001318836.2:c.188G>A
  • NM_001320717.2:c.548G>A
  • NM_001371443.1:c.548G>A
  • NM_001371444.1:c.548G>A
  • NM_001371446.1:c.548G>A
  • NM_001371447.1:c.548G>A
  • NM_001371448.1:c.548G>A
  • NM_001371449.1:c.548G>A
  • NM_001371450.1:c.548G>A
  • NM_001371451.1:c.188G>A
  • NM_001371452.1:c.47G>A
  • NM_001371453.1:c.47G>A
  • NM_001371454.1:c.47G>A
  • NM_001371455.1:c.47G>A
  • NM_001371456.1:c.47G>A
  • NM_001374085.1:c.548G>A
  • NM_001374086.1:c.47G>A
  • NM_004328.5:c.548G>A
  • NP_001073335.1:p.Arg183His
  • NP_001244271.1:p.Arg183His
  • NP_001244272.1:p.Arg183His
  • NP_001244273.1:p.Arg183His
  • NP_001305765.1:p.Arg63His
  • NP_001307646.1:p.Arg183His
  • NP_001358372.1:p.Arg183His
  • NP_001358373.1:p.Arg183His
  • NP_001358375.1:p.Arg183His
  • NP_001358376.1:p.Arg183His
  • NP_001358377.1:p.Arg183His
  • NP_001358378.1:p.Arg183His
  • NP_001358379.1:p.Arg183His
  • NP_001358380.1:p.Arg63His
  • NP_001358381.1:p.Arg16His
  • NP_001358382.1:p.Arg16His
  • NP_001358383.1:p.Arg16His
  • NP_001358384.1:p.Arg16His
  • NP_001358385.1:p.Arg16His
  • NP_001361014.1:p.Arg183His
  • NP_001361015.1:p.Arg16His
  • NP_004319.1:p.Arg183His
  • NP_004319.1:p.Arg183His
  • LRG_539t1:c.548G>A
  • LRG_539:g.7191G>A
  • LRG_539p1:p.Arg183His
  • NC_000002.11:g.219526569G>A
  • NM_004328.4:c.548G>A
  • NR_163955.1:n.1560G>A
  • Q9Y276:p.Arg183His
Protein change:
R16H; ARG183HIS
Links:
UniProtKB: Q9Y276#VAR_032089; OMIM: 603647.0008; dbSNP: rs121908577
NCBI 1000 Genomes Browser:
rs121908577
Molecular consequence:
  • NM_001079866.2:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257342.2:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257343.2:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257344.2:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318836.2:c.188G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320717.2:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371443.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371444.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371446.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371447.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371448.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371449.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371450.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371451.1:c.188G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371452.1:c.47G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371453.1:c.47G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371454.1:c.47G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371455.1:c.47G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371456.1:c.47G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374085.1:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374086.1:c.47G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004328.5:c.548G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_163955.1:n.1560G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Leigh syndrome (LS)
Synonyms:
Leigh Disease; Subacute necrotizing encephalopathy; Necrotizing encephalopathy infantile subacute of Leigh; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009723; MedGen: C0023264; Orphanet: 506; OMIM: 256000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000916675Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Feb 1, 2018)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Nuclear gene mutations as the cause of mitochondrial complex III deficiency.

Fernández-Vizarra E, Zeviani M.

Front Genet. 2015;6:134. doi: 10.3389/fgene.2015.00134. Review.

PubMed [citation]
PMID:
25914718
PMCID:
PMC4391031

Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome.

Hinson JT, Fantin VR, Schönberger J, Breivik N, Siem G, McDonough B, Sharma P, Keogh I, Godinho R, Santos F, Esparza A, Nicolau Y, Selvaag E, Cohen BH, Hoppel CL, Tranebjaerg L, Eavey RD, Seidman JG, Seidman CE.

N Engl J Med. 2007 Feb 22;356(8):809-19.

PubMed [citation]
PMID:
17314340
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000916675.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: BCS1L c.548G>A (p.Arg183His) results in a non-conservative amino acid change located in the N-terminal BCS1 domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 246466 control chromosomes. This frequency is not higher than expected for a pathogenic variant in BCS1L causing Bjornstad syndrome (1.6e-05 vs 0.00047), allowing no conclusion about variant significance. The c.548G>A variant has been reported in the literature in a consanguineous family with numerous affected individuals, all of whom were homozygous for the variant, inherited from heterozygous parents (Hinson_2007). These data indicate that the variant is very likely to be associated with disease. The same publication reports experimental complementation assays in yeast that showed a significant effect on protein function, where yeast growth rate was reduced to <10% of normal. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Additionally, a variant affecting the same codon (c.547C>T, p.Arg183Cys) is classified as pathogenic/likely pathogenic by multiple reputable clinical labs via ClinVar, supporting the functional impact of this position. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 24, 2022

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