rs368339692
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBS1BS2
The NM_020822.3(KCNT1):c.3437G>A(p.Arg1146His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,600,734 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1146C) has been classified as Uncertain significance.
Frequency
Consequence
NM_020822.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.3437G>A | p.Arg1146His | missense_variant | 29/31 | ENST00000371757.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.3437G>A | p.Arg1146His | missense_variant | 29/31 | 1 | NM_020822.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000375 AC: 81AN: 216266Hom.: 0 AF XY: 0.000574 AC XY: 69AN XY: 120122
GnomAD4 exome AF: 0.000253 AC: 366AN: 1448382Hom.: 1 Cov.: 36 AF XY: 0.000347 AC XY: 250AN XY: 719946
GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74500
ClinVar
Submissions by phenotype
KCNT1-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 21, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 27, 2020 | - - |
Developmental and epileptic encephalopathy, 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at