rs1553281318
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_020247.5(COQ8A):c.1744dupA(p.Ser582LysfsTer148) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S582S) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Consequence
COQ8A
NM_020247.5 frameshift
NM_020247.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.20
Genes affected
COQ8A (HGNC:16812): (coenzyme Q8A) This gene encodes a mitochondrial protein similar to yeast ABC1, which functions in an electron-transferring membrane protein complex in the respiratory chain. It is not related to the family of ABC transporter proteins. Expression of this gene is induced by the tumor suppressor p53 and in response to DNA damage, and inhibiting its expression partially suppresses p53-induced apoptosis. Alternatively spliced transcript variants have been found; however, their full-length nature has not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 12 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-226986536-G-GA is Pathogenic according to our data. Variant chr1-226986536-G-GA is described in ClinVar as [Pathogenic]. Clinvar id is 183336.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| COQ8A | ENST00000366777.4 | c.1744dupA | p.Ser582LysfsTer148 | frameshift_variant | Exon 15 of 15 | 1 | NM_020247.5 | ENSP00000355739.3 | ||
| ENSG00000288674 | ENST00000366779.6 | n.*6471dupA | non_coding_transcript_exon_variant | Exon 32 of 32 | 2 | ENSP00000355741.2 | ||||
| ENSG00000288674 | ENST00000366779.6 | n.*6471dupA | 3_prime_UTR_variant | Exon 32 of 32 | 2 | ENSP00000355741.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive ataxia due to ubiquinone deficiency Pathogenic:2
Sep 26, 2019
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Significance: Likely pathogenic
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Mar 26, 2024
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Cerebellar ataxia;C0028738:Nystagmus;C0234162:Dysmetria;C0234518:Slurred speech;C0234979:Dysdiadochokinesis;C0740279:Cerebellar atrophy;CN228312:Slightly reduced reflexes Pathogenic:1
Dec 01, 2014
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance: Likely pathogenic
Review Status: no assertion criteria provided
Collection Method: research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at