rs199832638
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_057176.3(BSND):c.806G>A(p.Arg269Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_057176.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BSND | NM_057176.3 | c.806G>A | p.Arg269Gln | missense_variant | 4/4 | ENST00000651561.1 | NP_476517.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BSND | ENST00000651561.1 | c.806G>A | p.Arg269Gln | missense_variant | 4/4 | NM_057176.3 | ENSP00000498282 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000120 AC: 30AN: 251042Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135744
GnomAD4 exome AF: 0.000141 AC: 206AN: 1461832Hom.: 0 Cov.: 31 AF XY: 0.000131 AC XY: 95AN XY: 727214
GnomAD4 genome AF: 0.000118 AC: 18AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74358
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 23, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 269 of the BSND protein (p.Arg269Gln). This variant is present in population databases (rs199832638, gnomAD 0.02%). 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: 504521). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 2024 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 19, 2017 | p.Arg269Gln in exon 4 of BSND: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, >10 mammals have a glutamine (Gln) at this position. In addition, computatio nal prediction tools do not suggest a high likelihood of impact to the protein. It has been identified in 10/66322 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs199832638). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at