ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs121908577
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779835 SCV000916675 pathogenic Leigh syndrome 2018-02-01 criteria provided, single submitter clinical testing 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002243624 SCV002512446 pathogenic Mitochondrial complex III deficiency nuclear type 1 2022-01-19 criteria provided, single submitter clinical testing ACMG classification criteria: PS3 supporting, PS4 strong, PM2 moderate, PM3 moderate, PP1 moderate, PP3 supporting
OMIM RCV000006545 SCV000026728 pathogenic Pili torti-deafness syndrome 2007-02-22 no assertion criteria provided literature only
Natera, Inc. RCV001835622 SCV002076351 pathogenic GRACILE syndrome 2021-07-06 no assertion criteria provided clinical testing

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