chr16-56865278-TTG-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001126108.2(SLC12A3):c.46_47del(p.Cys16GlnfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L15L) has been classified as Likely benign.
Frequency
Consequence
NM_001126108.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A3 | NM_001126108.2 | c.46_47del | p.Cys16GlnfsTer13 | frameshift_variant | 1/26 | ENST00000563236.6 | |
SLC12A3 | NM_000339.3 | c.46_47del | p.Cys16GlnfsTer13 | frameshift_variant | 1/26 | ||
SLC12A3 | NM_001126107.2 | c.46_47del | p.Cys16GlnfsTer13 | frameshift_variant | 1/26 | ||
SLC12A3 | NM_001410896.1 | c.46_47del | p.Cys16GlnfsTer13 | frameshift_variant | 1/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A3 | ENST00000563236.6 | c.46_47del | p.Cys16GlnfsTer13 | frameshift_variant | 1/26 | 1 | NM_001126108.2 | A1 | |
SLC12A3 | ENST00000438926.6 | c.46_47del | p.Cys16GlnfsTer13 | frameshift_variant | 1/26 | 1 | A1 | ||
SLC12A3 | ENST00000566786.5 | c.46_47del | p.Cys16GlnfsTer13 | frameshift_variant | 1/26 | 1 | P4 | ||
SLC12A3 | ENST00000262502.5 | c.46_47del | p.Cys16GlnfsTer13 | frameshift_variant | 1/26 | 5 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250758Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135668
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461580Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727112
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2023 | This sequence change creates a premature translational stop signal (p.Cys16Glnfs*13) in the SLC12A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC12A3 are known to be pathogenic (PMID: 20848653, 22009145, 25841442). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Gitelman syndrome (PMID: 8900229). 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