rs199624315
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_153033.5(KCTD7):c.362G>A(p.Arg121His) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,614,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign 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. R121C) has been classified as Uncertain significance.
Frequency
Consequence
NM_153033.5 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 |
---|---|---|---|---|---|---|---|
KCTD7 | NM_153033.5 | c.362G>A | p.Arg121His | missense_variant | 3/4 | ENST00000639828.2 | |
KCTD7 | NM_001167961.2 | c.362G>A | p.Arg121His | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCTD7 | ENST00000639828.2 | c.362G>A | p.Arg121His | missense_variant | 3/4 | 2 | NM_153033.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251460Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135910
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727248
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74480
ClinVar
Submissions by phenotype
Progressive myoclonic epilepsy type 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 121 of the KCTD7 protein (p.Arg121His). This variant is present in population databases (rs199624315, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with KCTD7-related conditions. ClinVar contains an entry for this variant (Variation ID: 469104). 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 KCTD7 protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at