15-48207769-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000338.3(SLC12A1):āc.50A>Gā(p.Asn17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000844 in 1,611,652 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Uncertain significance (ā ā ).
Frequency
Consequence
NM_000338.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC12A1 | NM_000338.3 | c.50A>G | p.Asn17Ser | missense_variant | 2/27 | ENST00000380993.8 | NP_000329.2 | |
SLC12A1 | NM_001184832.2 | c.50A>G | p.Asn17Ser | missense_variant | 2/27 | NP_001171761.1 | ||
SLC12A1 | NM_001384136.1 | c.50A>G | p.Asn17Ser | missense_variant | 2/27 | NP_001371065.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000803 AC: 20AN: 249064Hom.: 1 AF XY: 0.0000595 AC XY: 8AN XY: 134488
GnomAD4 exome AF: 0.0000795 AC: 116AN: 1459444Hom.: 1 Cov.: 31 AF XY: 0.0000772 AC XY: 56AN XY: 725702
GnomAD4 genome AF: 0.000131 AC: 20AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74368
ClinVar
Submissions by phenotype
SLC12A1-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 25, 2023 | The SLC12A1 c.50A>G variant is predicted to result in the amino acid substitution p.Asn17Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.044% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-48499966-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.50A>G (p.N17S) alteration is located in exon 2 (coding exon 1) of the SLC12A1 gene. This alteration results from a A to G substitution at nucleotide position 50, causing the asparagine (N) at amino acid position 17 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Bartter disease type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 07, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 06, 2024 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 17 of the SLC12A1 protein (p.Asn17Ser). This variant is present in population databases (rs757876818, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with SLC12A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2387586). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at