chr1-226961482-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020247.5(COQ8A):c.97G>A(p.Gly33Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,613,926 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G33G) has been classified as Likely benign.
Frequency
Consequence
NM_020247.5 missense
Scores
Clinical Significance
Conservation
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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.97G>A | p.Gly33Arg | missense_variant | 2/15 | ENST00000366777.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ8A | ENST00000366777.4 | c.97G>A | p.Gly33Arg | missense_variant | 2/15 | 1 | NM_020247.5 | P1 | |
COQ8A | ENST00000366778.5 | c.-34-26G>A | intron_variant | 1 | |||||
COQ8A | ENST00000489044.1 | n.308G>A | non_coding_transcript_exon_variant | 2/5 | 3 | ||||
COQ8A | ENST00000478406.5 | n.107-15967G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152274Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000275 AC: 69AN: 251078Hom.: 0 AF XY: 0.000346 AC XY: 47AN XY: 135808
GnomAD4 exome AF: 0.000144 AC: 210AN: 1461534Hom.: 0 Cov.: 31 AF XY: 0.000195 AC XY: 142AN XY: 727078
GnomAD4 genome AF: 0.0000656 AC: 10AN: 152392Hom.: 0 Cov.: 33 AF XY: 0.0000939 AC XY: 7AN XY: 74520
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 33 of the COQ8A protein (p.Gly33Arg). This variant is present in population databases (rs552784842, gnomAD 0.2%). 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: 214038). 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 expected to disrupt 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 | Sep 07, 2023 | In silico analysis supports that this missense 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