U.S. flag

An official website of the United States government

NM_001079866.2(BCS1L):c.871C>T (p.Arg291Ter) AND Pili torti-deafness syndrome

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Mar 12, 2024
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:
RCV000586158.9

Allele description [Variation Report for NM_001079866.2(BCS1L):c.871C>T (p.Arg291Ter)]

NM_001079866.2(BCS1L):c.871C>T (p.Arg291Ter)

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.871C>T (p.Arg291Ter)
Other names:
p.R291*:CGA>TGA
HGVS:
  • NC_000002.12:g.218662661C>T
  • NG_008018.1:g.8006C>T
  • NG_033099.1:g.1880G>A
  • NM_001079866.2:c.871C>TMANE SELECT
  • NM_001257342.2:c.871C>T
  • NM_001257343.2:c.871C>T
  • NM_001257344.2:c.871C>T
  • NM_001318836.2:c.511C>T
  • NM_001320717.2:c.871C>T
  • NM_001371443.1:c.871C>T
  • NM_001371444.1:c.871C>T
  • NM_001371446.1:c.871C>T
  • NM_001371447.1:c.871C>T
  • NM_001371448.1:c.871C>T
  • NM_001371449.1:c.871C>T
  • NM_001371450.1:c.871C>T
  • NM_001371451.1:c.511C>T
  • NM_001371452.1:c.370C>T
  • NM_001371453.1:c.370C>T
  • NM_001371454.1:c.370C>T
  • NM_001371455.1:c.370C>T
  • NM_001371456.1:c.370C>T
  • NM_001374085.1:c.871C>T
  • NM_001374086.1:c.370C>T
  • NM_004328.5:c.871C>T
  • NP_001073335.1:p.Arg291Ter
  • NP_001244271.1:p.Arg291Ter
  • NP_001244272.1:p.Arg291Ter
  • NP_001244273.1:p.Arg291Ter
  • NP_001305765.1:p.Arg171Ter
  • NP_001307646.1:p.Arg291Ter
  • NP_001358372.1:p.Arg291Ter
  • NP_001358373.1:p.Arg291Ter
  • NP_001358375.1:p.Arg291Ter
  • NP_001358376.1:p.Arg291Ter
  • NP_001358377.1:p.Arg291Ter
  • NP_001358378.1:p.Arg291Ter
  • NP_001358379.1:p.Arg291Ter
  • NP_001358380.1:p.Arg171Ter
  • NP_001358381.1:p.Arg124Ter
  • NP_001358382.1:p.Arg124Ter
  • NP_001358383.1:p.Arg124Ter
  • NP_001358384.1:p.Arg124Ter
  • NP_001358385.1:p.Arg124Ter
  • NP_001361014.1:p.Arg291Ter
  • NP_001361015.1:p.Arg124Ter
  • NP_004319.1:p.Arg291Ter
  • NP_004319.1:p.Arg291Ter
  • LRG_539t1:c.871C>T
  • LRG_539:g.8006C>T
  • LRG_539p1:p.Arg291Ter
  • NC_000002.11:g.219527384C>T
  • NM_001079866.1:c.871C>T
  • NM_004328.4:c.871C>T
  • NM_004328.5:c.871C>T
  • NR_163955.1:n.1878C>T
Protein change:
R124*
Links:
dbSNP: rs201454788
NCBI 1000 Genomes Browser:
rs201454788
Molecular consequence:
  • NR_163955.1:n.1878C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001079866.2:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001257342.2:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001257343.2:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001257344.2:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001318836.2:c.511C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001320717.2:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371443.1:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371444.1:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371446.1:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371447.1:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371448.1:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371449.1:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371450.1:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371451.1:c.511C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371452.1:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371453.1:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371454.1:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371455.1:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001371456.1:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374085.1:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374086.1:c.370C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004328.5:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Pili torti-deafness syndrome (BJS)
Synonyms:
Bjornstad syndrome; Pili torti and nerve deafness; Pili torti-sensorineural hearing loss; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009872; MedGen: C0266006; Orphanet: 123; OMIM: 262000

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000698305Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely pathogenic
(Nov 14, 2022)
germlineclinical testing

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

Citation Link,

SCV002503731Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Mar 30, 2023)
germlineclinical testing

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

SCV004210781Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Mar 12, 2024)
unknownclinical testing

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

Summary from all submissions

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

Citations

PubMed

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698305.5

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

Description

Variant summary: BCS1L c.871C>T (p.Arg291X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 250748 control chromosomes (gnomAD). c.871C>T has been reported in the literature in a compound heterozygote individual affected with Bjornstad syndrome (Hinson_2007). The authors of this study also reported experimental evidence evaluating an impact on protein function, demonstrating in a yeast complementation assay that the mutant protein failed to rescue growth on a medium that requires an active respiratory-chain. They also showed decreased electron-transport activities with increased production of reactive oxygen species in lymphocytes acquired from patients with Bjornstad syndrome and complex III deficiency (however, no patient specific data were provided, Hinson_2007). Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=1), likely pathogenic (n=1) and pathogenic (n=3). Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

From Molecular Genetics, Royal Melbourne Hospital, SCV002503731.2

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

Description

This sequence change creates a premature termination codon at position 291 in exon 7 (of 9) of BCS1L, p.(Arg291*). It is expected to result in an absent or disrupted protein product in a gene where loss of function is an established mechanism of disease. The variant is present in a large population cohort at a frequency of 0.003%, which is consistent with a recessive condition (rs201454788, 8/282,138 alleles, 0 homozygotes in gnomAD v2.1). The variant has been identified compound heterozygous with a second allele in a case diagnosed with Bjornstad syndrome (PMID: 17314340). Additionally, the variant demonstrates attenuated growth in a yeast complementation assay (PMID: 17314340). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM2, PS3_Supporting.

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

From Baylor Genetics, SCV004210781.2

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

Last Updated: Jun 17, 2024