rs1276883403
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2
The ENST00000371757.7(KCNT1):c.2848C>T(p.Arg950Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,606,224 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000371757.7 stop_gained
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNT1 | NM_020822.3 | c.2848C>T | p.Arg950Ter | stop_gained | 25/31 | ENST00000371757.7 | NP_065873.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNT1 | ENST00000371757.7 | c.2848C>T | p.Arg950Ter | stop_gained | 25/31 | 1 | NM_020822.3 | ENSP00000360822 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000409 AC: 1AN: 244232Hom.: 0 AF XY: 0.00000752 AC XY: 1AN XY: 132998
GnomAD4 exome AF: 0.00000344 AC: 5AN: 1453988Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2AN XY: 723700
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74362
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 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. ClinVar contains an entry for this variant (Variation ID: 473377). This variant has not been reported in the literature in individuals affected with KCNT1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg950*) in the KCNT1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in KCNT1 cause disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at