ClinVar Miner

Submissions for variant NM_003049.4(SLC10A1):c.755G>A (p.Arg252His)

gnomAD frequency: 0.00020  dbSNP: rs147226818
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000594593 SCV000708480 uncertain significance not provided 2017-05-08 criteria provided, single submitter clinical testing
3billion RCV001358772 SCV003841624 likely pathogenic Hypercholanemia, familial, 2 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.024%). Protein truncation variants are a common disease-causing mechanism. Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 24867799). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.87; 3Cnet: 0.11). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SLC10A1-related disorder (ClinVar ID: VCV000501945 / PMID: 24867799). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Molecular Genetics and NGS Laboratory, Hospital Fundacion Valle Del Lili RCV001358772 SCV004101390 pathogenic Hypercholanemia, familial, 2 2023-11-07 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV000594593 SCV005191456 uncertain significance not provided criteria provided, single submitter not provided
OMIM RCV001358772 SCV001554648 pathogenic Hypercholanemia, familial, 2 2021-04-07 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV003392438 SCV004110871 likely pathogenic SLC10A1-related disorder 2024-02-16 no assertion criteria provided clinical testing The SLC10A1 c.755G>A variant is predicted to result in the amino acid substitution p.Arg252His. This variant in the homozygous state has been reported in a patient with extremely elevated plasma bile salt levels, without clinical signs of pruritus, cholestasis, or liver dysfunction (Vaz et al. 2015. PubMed ID: 24867799; Vaz et al. 2017. PubMed ID: 28249272; Erlinger. 2015. PubMed ID: 25193235). Functional analysis showed that this variant resulted in a significantly reduced uptake activity of taurocholic acid (Vaz et al. 2015. PubMed ID: 24867799). This variant is reported in 0.042% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/). This variant is interpreted as likely pathogenic.

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