9-135784792-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_020822.3(KCNT1):c.3059G>A(p.Arg1020His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,612,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1020C) 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_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.3059G>A | p.Arg1020His | missense_variant | 27/31 | ENST00000371757.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.3059G>A | p.Arg1020His | missense_variant | 27/31 | 1 | NM_020822.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152120Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249494Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135258
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460502Hom.: 0 Cov.: 34 AF XY: 0.0000206 AC XY: 15AN XY: 726542
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152120Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74290
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 | May 22, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNT1 protein function. ClinVar contains an entry for this variant (Variation ID: 548573). This variant has not been reported in the literature in individuals affected with KCNT1-related conditions. This variant is present in population databases (rs373365707, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1020 of the KCNT1 protein (p.Arg1020His). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 27, 2020 | - - |
Developmental and epileptic encephalopathy, 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 14, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at