dbSNP rs2074930: COQ6:p.Asp339Ala (chr14-73961297-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182476.3(COQ6):c.1016A>C(p.Asp339Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D339G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

COQ6
NM_182476.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.99

Publications

26 publications found

Variant links:

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]

COQ6 links:

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]

ENTPD5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182476.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COQ6	NM_182476.3	MANE Select	c.1016A>C	p.Asp339Ala	missense	Exon 9 of 12	NP_872282.1
COQ6	NM_001425255.1		c.1016A>C	p.Asp339Ala	missense	Exon 9 of 11	NP_001412184.1
COQ6	NM_182480.3		c.941A>C	p.Asp314Ala	missense	Exon 9 of 12	NP_872286.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COQ6	ENST00000334571.7	TSL:1 MANE Select	c.1016A>C	p.Asp339Ala	missense	Exon 9 of 12	ENSP00000333946.2
COQ6	ENST00000554341.6	TSL:1	n.*621A>C		non_coding_transcript_exon	Exon 8 of 11	ENSP00000450736.2
COQ6	ENST00000554341.6	TSL:1	n.*621A>C		3_prime_UTR	Exon 8 of 11	ENSP00000450736.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.11

Eigen

Benign

-0.16

Eigen_PC

Benign

0.047

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

5.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

REVEL

Benign

0.10

Sift

Benign

0.70

Sift4G

Benign

0.78

Polyphen

0.017

Vest4

0.41

MutPred

0.32

Gain of MoRF binding (P = 0.0289)

MVP

0.56

MPC

0.85

ClinPred

0.90

GERP RS

5.3

Varity_R

0.13

gMVP

0.68

Mutation Taster

=40/60

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over