1-226982716-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_020247.5(COQ8A):āc.892G>Cā(p.Glu298Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,534 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E298K) has been classified as Uncertain significance.
Frequency
Consequence
NM_020247.5 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ8A | NM_020247.5 | c.892G>C | p.Glu298Gln | missense_variant | 7/15 | ENST00000366777.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ8A | ENST00000366777.4 | c.892G>C | p.Glu298Gln | missense_variant | 7/15 | 1 | NM_020247.5 | P1 | |
COQ8A | ENST00000366778.5 | c.736G>C | p.Glu246Gln | missense_variant | 7/15 | 1 | |||
COQ8A | ENST00000485462.5 | n.282G>C | non_coding_transcript_exon_variant | 3/11 | 1 | ||||
COQ8A | ENST00000478406.5 | n.871G>C | non_coding_transcript_exon_variant | 3/8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250876Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135792
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461368Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726986
GnomAD4 genome AF: 0.000118 AC: 18AN: 152166Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 298 of the COQ8A protein (p.Glu298Gln). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COQ8A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1312758). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COQ8A 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 01, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on 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