9-135786336-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_020822.3(KCNT1):c.3317G>C(p.Arg1106Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000694 in 1,441,676 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1106Q) has been classified as Likely benign.
Frequency
Consequence
NM_020822.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.3317G>C | p.Arg1106Pro | missense_variant | 29/31 | ENST00000371757.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.3317G>C | p.Arg1106Pro | missense_variant | 29/31 | 1 | NM_020822.3 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000503 AC: 1AN: 198616Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 109752
GnomAD4 exome AF: 0.00000694 AC: 10AN: 1441676Hom.: 0 Cov.: 36 AF XY: 0.00000419 AC XY: 3AN XY: 715244
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 17, 2017 | A variant of uncertain significance has been identified in the KCNT1 gene. The R1106P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R106P variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1106P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, a different missense variant at the same codon (R1106Q) have been reported in Human Gene Mutation Database in association with KCNT1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at