rs200246335
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_057176.3(BSND):āc.309G>Cā(p.Glu103Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000341 in 1,614,142 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_057176.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BSND | NM_057176.3 | c.309G>C | p.Glu103Asp | missense_variant | 3/4 | ENST00000651561.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BSND | ENST00000651561.1 | c.309G>C | p.Glu103Asp | missense_variant | 3/4 | NM_057176.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000394 AC: 60AN: 152162Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000438 AC: 110AN: 250988Hom.: 1 AF XY: 0.000464 AC XY: 63AN XY: 135788
GnomAD4 exome AF: 0.000335 AC: 490AN: 1461862Hom.: 5 Cov.: 33 AF XY: 0.000348 AC XY: 253AN XY: 727234
GnomAD4 genome ? AF: 0.000394 AC: 60AN: 152280Hom.: 1 Cov.: 32 AF XY: 0.000484 AC XY: 36AN XY: 74452
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 06, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2021 | The c.309G>C (p.E103D) alteration is located in exon 3 (coding exon 3) of the BSND gene. This alteration results from a G to C substitution at nucleotide position 309, causing the glutamic acid (E) at amino acid position 103 to be replaced by an aspartic acid (D). 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 | Jan 13, 2018 | 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 03, 2015 | p.Glu103Asp in exon 3 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, 3 mammals (microbat, hedehog and aardvark) have an aspartic acid (Asp) at th is position despite high nearby amino acid conservation. In addition, computatio nal prediction tools do not suggest a high likelihood of impact to the protein. The variant has also been identified in 54/65485 European chromosomes by the Exo me Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs2002463 35). - |
Bartter syndrome Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 30, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at