rs137853159
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000338.3(SLC12A1):c.1875G>A(p.Trp625Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,608 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000338.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A1 | NM_000338.3 | c.1875G>A | p.Trp625Ter | stop_gained | 15/27 | ENST00000380993.8 | |
SLC12A1 | NM_001184832.2 | c.1875G>A | p.Trp625Ter | stop_gained | 15/27 | ||
SLC12A1 | NM_001384136.1 | c.1875G>A | p.Trp625Ter | stop_gained | 15/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A1 | ENST00000380993.8 | c.1875G>A | p.Trp625Ter | stop_gained | 15/27 | 5 | NM_000338.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000315 AC: 48AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251118Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135706
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461456Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727018
GnomAD4 genome ? AF: 0.000315 AC: 48AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74332
ClinVar
Submissions by phenotype
SLC12A1-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 15, 2023 | The SLC12A1 c.1875G>A variant is predicted to result in premature protein termination (p.Trp625*). This variant was reported in the homozygous state in many Costa Rican patients with antenatal Bartter syndrome and is considered a founder variant in this population (Kurtz et al 1997. PubMed ID: 9355073).This variant is reported in 0.064% of alleles in individuals of Latino descent in gnomAD. Nonsense variants in SLC12A1 are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Bartter disease type 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1997 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2023 | This sequence change creates a premature translational stop signal (p.Trp625*) in the SLC12A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC12A1 are known to be pathogenic (PMID: 8640224, 9585600, 19096086). This variant is present in population databases (rs137853159, gnomAD 0.06%). This premature translational stop signal has been observed in individual(s) with Bartter syndrome (PMID: 9355073). ClinVar contains an entry for this variant (Variation ID: 8754). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at