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NM_001079866.2(BCS1L):c.217C>T (p.Arg73Cys) AND Mitochondrial complex III deficiency nuclear type 1

Clinical significance:Uncertain significance (Last evaluated: May 22, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000778591.2

Allele description [Variation Report for NM_001079866.2(BCS1L):c.217C>T (p.Arg73Cys)]

NM_001079866.2(BCS1L):c.217C>T (p.Arg73Cys)

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.217C>T (p.Arg73Cys)
HGVS:
  • NC_000002.12:g.218661204C>T
  • NG_008018.1:g.6549C>T
  • NG_033099.1:g.3337G>A
  • NM_001079866.2:c.217C>TMANE SELECT
  • NM_001257342.2:c.217C>T
  • NM_001257343.2:c.217C>T
  • NM_001257344.2:c.217C>T
  • NM_001318836.2:c.-40-202C>T
  • NM_001320717.2:c.217C>T
  • NM_001371443.1:c.217C>T
  • NM_001371444.1:c.217C>T
  • NM_001371446.1:c.217C>T
  • NM_001371447.1:c.217C>T
  • NM_001371448.1:c.217C>T
  • NM_001371449.1:c.217C>T
  • NM_001371450.1:c.217C>T
  • NM_001371451.1:c.-40-202C>T
  • NM_001371452.1:c.-41-555C>T
  • NM_001371453.1:c.-260C>T
  • NM_001371454.1:c.-260C>T
  • NM_001371455.1:c.-260C>T
  • NM_001371456.1:c.-260C>T
  • NM_001374085.1:c.217C>T
  • NM_001374086.1:c.-260C>T
  • NM_004328.5:c.217C>T
  • NP_001073335.1:p.Arg73Cys
  • NP_001244271.1:p.Arg73Cys
  • NP_001244272.1:p.Arg73Cys
  • NP_001244273.1:p.Arg73Cys
  • NP_001307646.1:p.Arg73Cys
  • NP_001358372.1:p.Arg73Cys
  • NP_001358373.1:p.Arg73Cys
  • NP_001358375.1:p.Arg73Cys
  • NP_001358376.1:p.Arg73Cys
  • NP_001358377.1:p.Arg73Cys
  • NP_001358378.1:p.Arg73Cys
  • NP_001358379.1:p.Arg73Cys
  • NP_001361014.1:p.Arg73Cys
  • NP_004319.1:p.Arg73Cys
  • NP_004319.1:p.Arg73Cys
  • LRG_539t1:c.217C>T
  • LRG_539:g.6549C>T
  • LRG_539p1:p.Arg73Cys
  • NC_000002.11:g.219525927C>T
  • NM_004328.4:c.217C>T
  • NR_163955.1:n.1229C>T
Protein change:
R73C
Links:
dbSNP: rs140812286
NCBI 1000 Genomes Browser:
rs140812286
Molecular consequence:
  • NM_001371453.1:c.-260C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371454.1:c.-260C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371455.1:c.-260C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371456.1:c.-260C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001374086.1:c.-260C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001318836.2:c.-40-202C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371451.1:c.-40-202C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371452.1:c.-41-555C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079866.2:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257342.2:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257343.2:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257344.2:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320717.2:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371443.1:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371444.1:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371446.1:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371447.1:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371448.1:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371449.1:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371450.1:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374085.1:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004328.5:c.217C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_163955.1:n.1229C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Mitochondrial complex III deficiency nuclear type 1
Synonyms:
Complex 3 mitochondrial respiratory chain deficiency
Identifiers:
MONDO: MONDO:0007415; MedGen: C3541471; Orphanet: 254902; OMIM: 124000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000914898Illumina Laboratory Services,Illuminacriteria provided, single submitter
Uncertain significance
(May 22, 2017)
germlineclinical testing

PubMed (2)
[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

Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cells.

Invernizzi F, D'Amato I, Jensen PB, Ravaglia S, Zeviani M, Tiranti V.

Mitochondrion. 2012 Mar;12(2):328-35. doi: 10.1016/j.mito.2012.01.001. Epub 2012 Jan 28.

PubMed [citation]
PMID:
22310368
PMCID:
PMC3314980

Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy.

Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero I, Zeviani M.

Hum Mol Genet. 2007 May 15;16(10):1241-52. Epub 2007 Apr 2.

PubMed [citation]
PMID:
17403714

Details of each submission

From Illumina Laboratory Services,Illumina, SCV000914898.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The BCS1L c.217C>T (p.Arg73Cys) variant has been reported in two studies in the same individual with mitochondrial respiratory chain complex III deficiency in a compound heterozygous state with another missense variant (Fernandez-Vizarra et al. 2007; Invernizzi et al. 2012). The p.Arg73Cys variant was absent from 210 control alleles, but is reported at a frequency of 0.00315 in the Ashkenazi Jewish population of the Genome Aggregation Database. The Arg73 residue is conserved across multiple species. Patient fibroblasts showed 30% residual enzyme activity and 50% maximum respiration rate compared to wild type (Invernizzi et al. 2012). Growth complementation studies in yeast showed that the p.Arg73Cys variant alone was insufficient to cause a growth defect, but in the presence of the other missense variant from the compound heterozygous patient, growth was significantly reduced compared to wild type. A similar result was obtained looking at the mitochondrial cytochrome profile and respiration activity (Fernandez-Vizarra et al. 2007; Invernizzi et al. 2012). The evidence for this variant is limited. The p.Arg73Cys variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for mitochondrial respiratory chain complex III deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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

Last Updated: Aug 23, 2022

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