chr1-226961452-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_020247.5(COQ8A):c.67G>A(p.Val23Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000881 in 1,613,846 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V23A) has been classified as Uncertain significance.
Frequency
Consequence
NM_020247.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COQ8A | ENST00000366777.4 | c.67G>A | p.Val23Met | missense_variant | Exon 2 of 15 | 1 | NM_020247.5 | ENSP00000355739.3 | ||
ENSG00000288674 | ENST00000366779.6 | n.*4794G>A | non_coding_transcript_exon_variant | Exon 19 of 32 | 2 | ENSP00000355741.2 | ||||
ENSG00000288674 | ENST00000366779.6 | n.*4794G>A | 3_prime_UTR_variant | Exon 19 of 32 | 2 | ENSP00000355741.2 |
Frequencies
GnomAD3 genomes AF: 0.000539 AC: 82AN: 152256Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000526 AC: 132AN: 251144Hom.: 1 AF XY: 0.000552 AC XY: 75AN XY: 135832
GnomAD4 exome AF: 0.000917 AC: 1340AN: 1461472Hom.: 2 Cov.: 31 AF XY: 0.000897 AC XY: 652AN XY: 727060
GnomAD4 genome AF: 0.000538 AC: 82AN: 152374Hom.: 0 Cov.: 33 AF XY: 0.000537 AC XY: 40AN XY: 74506
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
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Autosomal recessive ataxia due to ubiquinone deficiency Uncertain:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Inborn genetic diseases Uncertain:1
The c.67G>A (p.V23M) alteration is located in exon 2 (coding exon 1) of the COQ8A gene. This alteration results from a G to A substitution at nucleotide position 67, causing the valine (V) at amino acid position 23 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not specified Benign:1
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at