rs397515406
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM2PP3_ModeratePP5_Very_Strong
The NM_020822.3(KCNT1):c.2386T>C(p.Tyr796His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y796C) has been classified as Uncertain significance.
Frequency
Consequence
NM_020822.3 missense
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 |
---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.2386T>C | p.Tyr796His | missense_variant | 21/31 | ENST00000371757.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.2386T>C | p.Tyr796His | missense_variant | 21/31 | 1 | NM_020822.3 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Autosomal dominant nocturnal frontal lobe epilepsy 5 Pathogenic:2Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2012 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Likely pathogenic, criteria provided, single submitter | research | Duke University Health System Sequencing Clinic, Duke University Health System | Apr 20, 2023 | - - |
Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 08, 2018 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change alters the channels activity (PMID: 24591078, 26269628). This variant has been observed to be de novo in several individuals affected with epileptic encephalopathy (PMID: 26369628, 29186148, 25590979) and reported to segregate in a family affected with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (PMID: 23086396) . ClinVar contains an entry for this variant (Variation ID: 39598). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 796 of the KCNT1 protein (p.Tyr796His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at