rs765966679
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020247.5(COQ8A):c.337G>A(p.Glu113Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_020247.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ8A | NM_020247.5 | c.337G>A | p.Glu113Lys | missense_variant | 3/15 | ENST00000366777.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ8A | ENST00000366777.4 | c.337G>A | p.Glu113Lys | missense_variant | 3/15 | 1 | NM_020247.5 | P1 | |
COQ8A | ENST00000366778.5 | c.181G>A | p.Glu61Lys | missense_variant | 3/15 | 1 | |||
COQ8A | ENST00000489044.1 | n.548G>A | non_coding_transcript_exon_variant | 3/5 | 3 | ||||
COQ8A | ENST00000478406.5 | n.107-12290G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250754Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135748
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461488Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727046
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 31, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2022 | 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. 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 COQ8A protein function. ClinVar contains an entry for this variant (Variation ID: 446799). This variant has not been reported in the literature in individuals affected with COQ8A-related conditions. This variant is present in population databases (rs765966679, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 113 of the COQ8A protein (p.Glu113Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at