chr1-55008524-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_057176.3(BSND):c.859G>T(p.Glu287Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. E287E) has been classified as Likely benign.
Frequency
Consequence
NM_057176.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BSND | NM_057176.3 | c.859G>T | p.Glu287Ter | stop_gained | 4/4 | ENST00000651561.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BSND | ENST00000651561.1 | c.859G>T | p.Glu287Ter | stop_gained | 4/4 | NM_057176.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251428Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727228
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 28, 2016 | The p.Glu287X variant in BSND has not been previously reported in individuals wi th hearing loss or Bartter syndrome, but has been identified in 1/66718 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs376784896). Although this variant has been seen in the general p opulation, its frequency is not high enough to rule out a pathogenic role. This nonsense variant leads to a premature termination codon at position 287. This al teration occurs within the last exon and is likely to escape nonsense mediated d ecay (NMD) and to result in a truncated product 10% shorter than the normal prot ein. It is unclear whether the truncation impacts the protein function. In summa ry, the clinical significance of the p.Glu287X variant is uncertain. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2021 | The c.859G>T (p.E287*) alteration, located in exon 4 (coding exon 4) of the BSND gene, consists of a G to T substitution at nucleotide position 859. This changes the amino acid from a glutamic acid (E) to a stop codon at amino acid position 287. Premature stop codons are typically deleterious in nature (Richards, 2015). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Bartter disease type 4A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Dec 15, 2018 | This variant is a stop-gained variant, which was observed by ICSL 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 for this variant, it 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. No publications were found based on this search. This variant is located in the last exon or in the last 50 bp of the penultimate exon and may escape nonsense-mediated decay. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change creates a premature translational stop signal (p.Glu287*) in the BSND gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 34 amino acid(s) of the BSND protein. This variant is present in population databases (rs376784896, gnomAD 0.0009%). 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: 505171). 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. - |
Bartter syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 15, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at