chr14-73958990-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_182476.3(COQ6):c.632A>G(p.Asn211Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
COQ6
NM_182476.3 missense
NM_182476.3 missense
Scores
3
8
6
Clinical Significance
Conservation
PhyloP100: 8.46
Genes affected
COQ6 (HGNC:20233): (coenzyme Q6, monooxygenase) The protein encoded by this gene belongs to the ubiH/COQ6 family. It is an evolutionarily conserved monooxygenase required for the biosynthesis of coenzyme Q10 (or ubiquinone), which is an essential component of the mitochondrial electron transport chain, and one of the most potent lipophilic antioxidants implicated in the protection of cell damage by reactive oxygen species. Knockdown of this gene in mouse and zebrafish results in decreased growth due to increased apoptosis. Mutations in this gene are associated with autosomal recessive coenzyme Q10 deficiency-6 (COQ10D6), which manifests as nephrotic syndrome with sensorineural deafness. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2012]
ENTPD5 (HGNC:3367): (ectonucleoside triphosphate diphosphohydrolase 5 (inactive)) The protein encoded by this gene is similar to E-type nucleotidases (NTPases)/ecto-ATPase/apyrases. NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD5 contains 4 apyrase-conserved regions which is characteristic of NTPases. [provided by RefSeq, Jan 2009]
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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 |
---|---|---|---|---|---|---|---|
COQ6 | NM_182476.3 | c.632A>G | p.Asn211Ser | missense_variant | 6/12 | ENST00000334571.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ6 | ENST00000334571.7 | c.632A>G | p.Asn211Ser | missense_variant | 6/12 | 1 | NM_182476.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251456Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461728Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 2AN XY: 727172
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74288
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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 | Apr 04, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 211 of the COQ6 protein (p.Asn211Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with COQ6-related conditions. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
0.42, 0.91
.;.;B;P
Vest4
MutPred
0.71
.;.;Gain of disorder (P = 0.037);.;
MVP
MPC
0.59
ClinPred
D
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