9-135777491-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020822.3(KCNT1):c.2503G>A(p.Val835Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,380 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 (★). Synonymous variant affecting the same amino acid position (i.e. V835V) has been classified as Likely benign.
Frequency
Consequence
NM_020822.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.2503G>A | p.Val835Met | missense_variant | 21/31 | ENST00000371757.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.2503G>A | p.Val835Met | missense_variant | 21/31 | 1 | NM_020822.3 | A2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249658Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135238
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461380Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1AN XY: 726998
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2018 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with KCNT1-related disease. This variant is present in population databases (rs753584318, ExAC 0.002%). This sequence change replaces valine with methionine at codon 835 of the KCNT1 protein (p.Val835Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at