rs745917176
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_153033.5(KCTD7):c.506G>A(p.Arg169Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000083 in 1,613,952 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 Uncertain significance (★★).
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.506G>A | p.Arg169Gln | missense_variant | Exon 4 of 4 | ENST00000639828.2 | NP_694578.1 | |
KCTD7 | NM_001167961.2 | c.506G>A | p.Arg169Gln | 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.506G>A | p.Arg169Gln | missense_variant | Exon 4 of 4 | 2 | NM_153033.5 | ENSP00000492240.1 | ||
ENSG00000284461 | ENST00000503687.2 | n.336G>A | non_coding_transcript_exon_variant | Exon 3 of 13 | 2 | ENSP00000421074.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251132Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135788
GnomAD4 exome AF: 0.0000882 AC: 129AN: 1461788Hom.: 0 Cov.: 32 AF XY: 0.0000880 AC XY: 64AN XY: 727206
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
not specified Uncertain:1
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Progressive myoclonic epilepsy type 3 Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 169 of the KCTD7 protein (p.Arg169Gln). This variant is present in population databases (rs745917176, gnomAD 0.006%). 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: 423509). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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
A variant of uncertain significance has been identified in the KCTD7 gene. The R169Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R169Q 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 R169Q variant is a a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, 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