rs552465571
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_020312.4(COQ9):c.841A>G(p.Met281Val) variant causes a missense change. The variant allele was found at a frequency of 0.00013 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000088 ( 0 hom. )
Consequence
COQ9
NM_020312.4 missense
NM_020312.4 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 6.15
Genes affected
COQ9 (HGNC:25302): (coenzyme Q9) This locus represents a mitochondrial ubiquinone biosynthesis gene. The encoded protein is likely necessary for biosynthesis of coenzyme Q10, as mutations at this locus have been associated with autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.041945398).
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000539 (82/152164) while in subpopulation AMR AF= 0.00478 (73/15284). AF 95% confidence interval is 0.00389. There are 0 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ9 | NM_020312.4 | c.841A>G | p.Met281Val | missense_variant | 7/9 | ENST00000262507.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ9 | ENST00000262507.11 | c.841A>G | p.Met281Val | missense_variant | 7/9 | 1 | NM_020312.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000539 AC: 82AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000179 AC: 45AN: 251438Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135896
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GnomAD4 exome AF: 0.0000876 AC: 128AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000880 AC XY: 64AN XY: 727242
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GnomAD4 genome ? AF: 0.000539 AC: 82AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.000726 AC XY: 54AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 281 of the COQ9 protein (p.Met281Val). This variant is present in population databases (rs552465571, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with COQ9-related conditions. ClinVar contains an entry for this variant (Variation ID: 376877). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 30, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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