chr9-135786336-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_020822.3(KCNT1):c.3317G>A(p.Arg1106Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,593,924 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1106W) has been classified as Uncertain significance.
Frequency
Consequence
NM_020822.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.3317G>A | p.Arg1106Gln | missense_variant | 29/31 | ENST00000371757.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.3317G>A | p.Arg1106Gln | missense_variant | 29/31 | 1 | NM_020822.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152132Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000388 AC: 77AN: 198616Hom.: 0 AF XY: 0.000337 AC XY: 37AN XY: 109752
GnomAD4 exome AF: 0.000163 AC: 235AN: 1441676Hom.: 0 Cov.: 36 AF XY: 0.000169 AC XY: 121AN XY: 715244
GnomAD4 genome AF: 0.000230 AC: 35AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74446
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 11, 2021 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 27, 2021 | This variant is associated with the following publications: (PMID: 32883383, 30821013, 29870100, 30662450, 26740507, 25339316, 31872048) - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | KCNT1: BS1, BS2 - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 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. - |
KCNT1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 24, 2023 | 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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy 5 Benign:1
Likely 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