rs1554774904
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020822.3(KCNT1):āc.1748C>Gā(p.Ala583Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,012 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A583V) has been classified as Uncertain significance.
Frequency
Consequence
NM_020822.3 missense
Scores
Clinical Significance
Conservation
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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.1748C>G | p.Ala583Gly | missense_variant | 17/31 | ENST00000371757.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.1748C>G | p.Ala583Gly | missense_variant | 17/31 | 1 | NM_020822.3 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460012Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726308
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 | Feb 22, 2020 | This variant has not been reported in the literature in individuals with KCNT1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with glycine at codon 583 of the KCNT1 protein (p.Ala583Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. 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: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at