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NM_001079866.2(BCS1L):c.134G>A (p.Arg45His) AND not provided

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Dec 11, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001243753.15

Allele description [Variation Report for NM_001079866.2(BCS1L):c.134G>A (p.Arg45His)]

NM_001079866.2(BCS1L):c.134G>A (p.Arg45His)

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.134G>A (p.Arg45His)
HGVS:
  • NC_000002.12:g.218661121G>A
  • NG_008018.1:g.6466G>A
  • NG_033099.1:g.3420C>T
  • NM_001079866.2:c.134G>AMANE SELECT
  • NM_001257342.2:c.134G>A
  • NM_001257343.2:c.134G>A
  • NM_001257344.2:c.134G>A
  • NM_001318836.2:c.-40-285G>A
  • NM_001320717.2:c.134G>A
  • NM_001371443.1:c.134G>A
  • NM_001371444.1:c.134G>A
  • NM_001371446.1:c.134G>A
  • NM_001371447.1:c.134G>A
  • NM_001371448.1:c.134G>A
  • NM_001371449.1:c.134G>A
  • NM_001371450.1:c.134G>A
  • NM_001371451.1:c.-40-285G>A
  • NM_001371452.1:c.-41-638G>A
  • NM_001371453.1:c.-343G>A
  • NM_001371454.1:c.-343G>A
  • NM_001371455.1:c.-343G>A
  • NM_001371456.1:c.-343G>A
  • NM_001374085.1:c.134G>A
  • NM_001374086.1:c.-343G>A
  • NM_004328.5:c.134G>A
  • NP_001073335.1:p.Arg45His
  • NP_001244271.1:p.Arg45His
  • NP_001244272.1:p.Arg45His
  • NP_001244273.1:p.Arg45His
  • NP_001307646.1:p.Arg45His
  • NP_001358372.1:p.Arg45His
  • NP_001358373.1:p.Arg45His
  • NP_001358375.1:p.Arg45His
  • NP_001358376.1:p.Arg45His
  • NP_001358377.1:p.Arg45His
  • NP_001358378.1:p.Arg45His
  • NP_001358379.1:p.Arg45His
  • NP_001361014.1:p.Arg45His
  • NP_004319.1:p.Arg45His
  • NP_004319.1:p.Arg45His
  • LRG_539t1:c.134G>A
  • LRG_539:g.6466G>A
  • LRG_539p1:p.Arg45His
  • NC_000002.11:g.219525844G>A
  • NM_004328.4:c.134G>A
  • NR_163955.1:n.1146G>A
Protein change:
R45H
Links:
dbSNP: rs754414354
NCBI 1000 Genomes Browser:
rs754414354
Molecular consequence:
  • NM_001371453.1:c.-343G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371454.1:c.-343G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371455.1:c.-343G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001371456.1:c.-343G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001374086.1:c.-343G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001318836.2:c.-40-285G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371451.1:c.-40-285G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371452.1:c.-41-638G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079866.2:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257342.2:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257343.2:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001257344.2:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320717.2:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371443.1:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371444.1:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371446.1:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371447.1:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371448.1:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371449.1:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371450.1:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374085.1:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004328.5:c.134G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_163955.1:n.1146G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001416934Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 11, 2023)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002504356GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Likely pathogenic
(Mar 10, 2022)
germlineclinical testing

Citation Link,

SCV003819585Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jun 3, 2022)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Novel compound heterozygous mutations in BCS1L gene causing Bjornstad syndrome in two siblings.

Falco M, Franzè A, Iossa S, De Falco L, Gambale A, Marciano E, Iolascon A.

Am J Med Genet A. 2017 May;173(5):1348-1352. doi: 10.1002/ajmg.a.38146. Epub 2017 Mar 21.

PubMed [citation]
PMID:
28322498

Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.

De Meirleir L, Seneca S, Damis E, Sepulchre B, Hoorens A, Gerlo E, García Silva MT, Hernandez EM, Lissens W, Van Coster R.

Am J Med Genet A. 2003 Aug 30;121A(2):126-31.

PubMed [citation]
PMID:
12910490
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001416934.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 45 of the BCS1L protein (p.Arg45His). This variant is present in population databases (rs754414354, gnomAD 0.004%). This missense change has been observed in individual(s) with Bjornstad syndrome (PMID: 28322498). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 554577). 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 with a positive predictive value of 95%. This variant disrupts the p.Arg45 amino acid residue in BCS1L. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12910490, 20727375). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

From GeneDx, SCV002504356.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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: 28322498)

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

From Revvity Omics, Revvity, SCV003819585.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 15, 2024