20-45097738-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001322799.2(KCNS1):c.1034G>A(p.Arg345His) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging 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.1034G>A | p.Arg345His | missense_variant | Exon 3 of 4 | 1 | NM_001322799.2 | ENSP00000445595.1 | ||
KCNS1 | ENST00000306117.5 | c.1034G>A | p.Arg345His | missense_variant | Exon 4 of 5 | 1 | ENSP00000307694.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152266Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152384Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74530
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1034G>A (p.R345H) alteration is located in exon 4 (coding exon 2) of the KCNS1 gene. This alteration results from a G to A substitution at nucleotide position 1034, causing the arginine (R) at amino acid position 345 to be replaced by a histidine (H). 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