NM_001079866.2(BCS1L):c.268C>T (p.Arg90Cys) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 4, 2023
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:: RCV001855960.6

Allele description [Variation Report for NM_001079866.2(BCS1L):c.268C>T (p.Arg90Cys)]

NM_001079866.2(BCS1L):c.268C>T (p.Arg90Cys)

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.268C>T (p.Arg90Cys)

HGVS:

NC_000002.12:g.218661255C>T
NG_008018.1:g.6600C>T
NG_033099.1:g.3286G>A
NM_001079866.2:c.268C>TMANE SELECT
NM_001257342.2:c.268C>T
NM_001257343.2:c.268C>T
NM_001257344.2:c.268C>T
NM_001318836.2:c.-40-151C>T
NM_001320717.2:c.268C>T
NM_001371443.1:c.268C>T
NM_001371444.1:c.268C>T
NM_001371446.1:c.268C>T
NM_001371447.1:c.268C>T
NM_001371448.1:c.268C>T
NM_001371449.1:c.268C>T
NM_001371450.1:c.268C>T
NM_001371451.1:c.-40-151C>T
NM_001371452.1:c.-41-504C>T
NM_001371453.1:c.-209C>T
NM_001371454.1:c.-209C>T
NM_001371455.1:c.-209C>T
NM_001371456.1:c.-209C>T
NM_001374085.1:c.268C>T
NM_001374086.1:c.-209C>T
NM_004328.5:c.268C>T
NP_001073335.1:p.Arg90Cys
NP_001244271.1:p.Arg90Cys
NP_001244272.1:p.Arg90Cys
NP_001244273.1:p.Arg90Cys
NP_001307646.1:p.Arg90Cys
NP_001358372.1:p.Arg90Cys
NP_001358373.1:p.Arg90Cys
NP_001358375.1:p.Arg90Cys
NP_001358376.1:p.Arg90Cys
NP_001358377.1:p.Arg90Cys
NP_001358378.1:p.Arg90Cys
NP_001358379.1:p.Arg90Cys
NP_001361014.1:p.Arg90Cys
NP_004319.1:p.Arg90Cys
NP_004319.1:p.Arg90Cys
LRG_539t1:c.268C>T
LRG_539:g.6600C>T
LRG_539p1:p.Arg90Cys
NC_000002.11:g.219525978C>T
NM_001079866.1:c.268C>T
NM_004328.4:c.268C>T
NR_163955.1:n.1280C>T

Protein change:

R90C

Links:

dbSNP: rs369691608

NCBI 1000 Genomes Browser:

rs369691608

Molecular consequence:

NM_001371453.1:c.-209C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001371454.1:c.-209C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001371455.1:c.-209C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001371456.1:c.-209C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374086.1:c.-209C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001318836.2:c.-40-151C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001371451.1:c.-40-151C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001371452.1:c.-41-504C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001079866.2:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257342.2:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257343.2:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001257344.2:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001320717.2:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371443.1:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371444.1:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371446.1:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371447.1:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371448.1:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371449.1:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001371450.1:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001374085.1:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004328.5:c.268C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_163955.1:n.1280C>T - 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
SCV002309702	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 4, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 34650211, 22277967, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002309702

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 4, 2023)

germline

clinical testing

PubMed (3)
[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

BCS1L mutations produce Fanconi syndrome with developmental disability.

Kanako KI, Sakakibara N, Murayama K, Nagatani K, Murata S, Otake A, Koga Y, Suzuki H, Uehara T, Kosaki K, Yoshiura KI, Mishima H, Ichimiya Y, Mushimoto Y, Horinouchi T, Nagano C, Yamamura T, Iijima K, Nozu K.

J Hum Genet. 2022 Mar;67(3):143-148. doi: 10.1038/s10038-021-00984-0. Epub 2021 Oct 15.

PubMed [citation]

PMID:: 34650211

Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing.

Calvo SE, Compton AG, Hershman SG, Lim SC, Lieber DS, Tucker EJ, Laskowski A, Garone C, Liu S, Jaffe DB, Christodoulou J, Fletcher JM, Bruno DL, Goldblatt J, Dimauro S, Thorburn DR, Mootha VK.

Sci Transl Med. 2012 Jan 25;4(118):118ra10. doi: 10.1126/scitranslmed.3003310.

PubMed [citation]

PMID:: 22277967
PMCID:: PMC3523805

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002309702.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 90 of the BCS1L protein (p.Arg90Cys). This variant is present in population databases (rs369691608, gnomAD 0.003%). This missense change has been observed in individual(s) with BCS1L-related conditions (PMID: 22277967, 34650211). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 625207). 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 missense change affects BCS1L function (PMID: 22277967). For these reasons, this variant has been classified as Pathogenic.

#	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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