chr16-57447510-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020312.4(COQ9):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000957 in 1,149,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
COQ9
NM_020312.4 missense
NM_020312.4 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 2.61
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ9 | NM_020312.4 | c.5C>T | p.Ala2Val | missense_variant | 1/9 | ENST00000262507.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ9 | ENST00000262507.11 | c.5C>T | p.Ala2Val | missense_variant | 1/9 | 1 | NM_020312.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD4 exome AF: 0.00000957 AC: 11AN: 1149068Hom.: 0 Cov.: 32 AF XY: 0.0000108 AC XY: 6AN XY: 553252
GnomAD4 exome
AF:
AC:
11
AN:
1149068
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
553252
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 20, 2021 | This variant has not been reported in the literature in individuals with COQ9-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces alanine with valine at codon 2 of the COQ9 protein (p.Ala2Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.
MutationTaster
Benign
D;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
P;.;.;.;.
Vest4
MutPred
Gain of stability (P = 0.0402);Gain of stability (P = 0.0402);Gain of stability (P = 0.0402);Gain of stability (P = 0.0402);Gain of stability (P = 0.0402);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at