NM_153033.5:c.790A>C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_153033.5(KCTD7):c.790A>C(p.Ile264Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I264I) has been classified as Likely benign.
Frequency
Consequence
NM_153033.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCTD7 | NM_153033.5 | c.790A>C | p.Ile264Leu | missense_variant | Exon 4 of 4 | ENST00000639828.2 | NP_694578.1 | |
KCTD7 | NM_001167961.2 | c.790A>C | p.Ile264Leu | missense_variant | Exon 4 of 5 | NP_001161433.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCTD7 | ENST00000639828.2 | c.790A>C | p.Ile264Leu | missense_variant | Exon 4 of 4 | 2 | NM_153033.5 | ENSP00000492240.1 | ||
ENSG00000284461 | ENST00000503687.2 | n.397+223A>C | intron_variant | Intron 3 of 12 | 2 | ENSP00000421074.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Progressive myoclonic epilepsy type 3 Uncertain:1
This sequence change replaces isoleucine with leucine at codon 264 of the KCTD7 protein (p.Ile264Leu). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCTD7-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at