rs199696535
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_057176.3(BSND):āc.770A>Gā(p.Gln257Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,614,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_057176.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BSND | NM_057176.3 | c.770A>G | p.Gln257Arg | missense_variant | 4/4 | ENST00000651561.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BSND | ENST00000651561.1 | c.770A>G | p.Gln257Arg | missense_variant | 4/4 | NM_057176.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251176Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135798
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 727224
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152368Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74508
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2022 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 257 of the BSND protein (p.Gln257Arg). This variant is present in population databases (rs199696535, 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: 517488). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 31, 2022 | Reported without a second variant in a patient with Dent disease in published literature (Cogal et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34805638) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 13, 2017 | The p.Gln257Arg variant in BSND has not been previously reported in individuals with hearing loss, but has been reported in 21/34412 Latino chromosomes by the G enome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs19 9696535). Although this variant has been seen in the general population, its fre quency is not high enough to rule out a pathogenic role. Computational predictio n tools and conservation analyses suggest that this variant may not impact the p rotein, though this information is not predictive enough to rule out pathogenici ty. In summary, the clinical significance of the p.Gln257Arg variant is uncertai n. - |
Bartter disease type 4A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 04, 2022 | - - |
Bartter syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at