rs1554774322
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_020822.3(KCNT1):c.1406A>C(p.His469Pro) variant causes a missense change. 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. H469Q) has been classified as Likely benign.
Frequency
Consequence
NM_020822.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.1406A>C | p.His469Pro | missense_variant | 15/31 | ENST00000371757.7 | NP_065873.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.1406A>C | p.His469Pro | missense_variant | 15/31 | 1 | NM_020822.3 | ENSP00000360822.2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 14 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | Oct 02, 2021 | It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.His469Leu) has been reported as pathogenic/likely pathogenic (VCV000496671.1 PM5). Missense changes are a common disease-causing mechanism (PP2). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.641, 3Cnet: 0.907, PP3). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.