20-45095212-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001322799.2(KCNS1):c.1239G>T(p.Trp413Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,062 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 (★).
Frequency
Consequence
NM_001322799.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNS1 | ENST00000537075.3 | c.1239G>T | p.Trp413Cys | missense_variant | Exon 4 of 4 | 1 | NM_001322799.2 | ENSP00000445595.1 | ||
KCNS1 | ENST00000306117.5 | c.1239G>T | p.Trp413Cys | missense_variant | Exon 5 of 5 | 1 | ENSP00000307694.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251366Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135872
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10AN XY: 727238
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1239G>T (p.W413C) alteration is located in exon 5 (coding exon 3) of the KCNS1 gene. This alteration results from a G to T substitution at nucleotide position 1239, causing the tryptophan (W) at amino acid position 413 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at