rs759470563
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020247.5(COQ8A):āc.1097A>Gā(p.Gln366Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,806 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 ).
Frequency
Genomes: š 0.000059 ( 0 hom., cov: 33)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
COQ8A
NM_020247.5 missense
NM_020247.5 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 7.43
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2677288).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COQ8A | NM_020247.5 | c.1097A>G | p.Gln366Arg | missense_variant | 9/15 | ENST00000366777.4 | NP_064632.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COQ8A | ENST00000366777.4 | c.1097A>G | p.Gln366Arg | missense_variant | 9/15 | 1 | NM_020247.5 | ENSP00000355739.3 | ||
ENSG00000288674 | ENST00000366779.6 | n.*5824A>G | non_coding_transcript_exon_variant | 26/32 | 2 | ENSP00000355741.2 | ||||
ENSG00000288674 | ENST00000366779.6 | n.*5824A>G | 3_prime_UTR_variant | 26/32 | 2 | ENSP00000355741.2 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251250Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135886
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461592Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727102
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74366
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 21, 2022 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 366 of the COQ8A protein (p.Gln366Arg). This variant is present in population databases (rs759470563, gnomAD 0.02%). 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: 585373). 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. 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 | Feb 16, 2022 | 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 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 21, 2017 | - - |
Autosomal recessive ataxia due to ubiquinone deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 09, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;B
Vest4
MutPred
Gain of MoRF binding (P = 0.0159);.;Gain of MoRF binding (P = 0.0159);
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at