Submissions for variant NM_057176.3(BSND):c.393G>T (p.Leu131Phe)

dbSNP: rs201387711

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001097209	SCV001253468	uncertain significance	Bartter disease type 4A	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV001195414	SCV001365765	uncertain significance	not specified	2019-11-26	criteria provided, single submitter	clinical testing	The p.Leu131Phe variant in BSND has not been previously reported in individuals with hearing loss and renal dysfunction but has been identified in 0.058% (6/10368) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3.
GeneDx	RCV001732040	SCV001982951	uncertain significance	not provided	2021-04-19	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Invitae	RCV001732040	SCV003515821	uncertain significance	not provided	2022-08-29	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 131 of the BSND protein (p.Leu131Phe). This variant is present in population databases (rs201387711, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with BSND-related conditions. ClinVar contains an entry for this variant (Variation ID: 874344). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc.	RCV001836120	SCV002092695	uncertain significance	Bartter syndrome	2020-01-17	no assertion criteria provided	clinical testing