14-73961297-A-T

Position:

chr14-73961297-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182476.3(COQ6):c.1016A>T(p.Asp339Val) variant causes a missense change. The variant allele was found at a frequency of 0.0599 in 1,614,026 control chromosomes in the GnomAD database, including 5,430 homozygotes. 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.085 ( 908 hom., cov: 32)

Exomes 𝑓: 0.057 ( 4522 hom. )

Consequence

COQ6
NM_182476.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.99

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:

COQ6 (HGNC:):

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014210045).

BP6

Variant 14-73961297-A-T is Benign according to our data. Variant chr14-73961297-A-T is described in ClinVar as [Benign]. Clinvar id is 128833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73961297-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ6	NM_182476.3 linkuse as main transcript	c.1016A>T	p.Asp339Val	missense_variant	9/12	ENST00000334571.7	NP_872282.1	Q9Y2Z9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ6	ENST00000334571.7 linkuse as main transcript	c.1016A>T	p.Asp339Val	missense_variant	9/12	1	NM_182476.3	ENSP00000333946.2		Q9Y2Z9-1

Frequencies

GnomAD3 genomes

AF:

0.0846

AC:

12869

AN:

152036

Hom.:

906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.0652

GnomAD3 exomes

AF:

0.0784

AC:

19701

AN:

251402

Hom.:

1699

AF XY:

0.0762

AC XY:

10359

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.0423

Gnomad ASJ exome

AF:

0.0288

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0152

Gnomad NFE exome

AF:

0.0413

Gnomad OTH exome

AF:

0.0486

GnomAD4 exome

AF:

0.0573

AC:

83768

AN:

1461872

Hom.:

4522

Cov.:

AF XY:

0.0583

AC XY:

42382

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.0437

Gnomad4 ASJ exome

AF:

0.0300

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.0163

Gnomad4 NFE exome

AF:

0.0429

Gnomad4 OTH exome

AF:

0.0621

GnomAD4 genome

AF:

0.0848

AC:

12898

AN:

152154

Hom.:

908

Cov.:

AF XY:

0.0850

AC XY:

6321

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.0454

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.321

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.0674

Alfa

AF:

0.0529

Hom.:

328

Bravo

AF:

0.0927

TwinsUK

AF:

0.0426

AC:

158

ALSPAC

AF:

0.0415

AC:

160

ESP6500AA

AF:

0.152

AC:

668

ESP6500EA

AF:

0.0430

AC:

370

ExAC

AF:

0.0818

AC:

9934

Asia WGS

AF:

0.175

AC:

605

AN:

3478

EpiCase

AF:

0.0377

EpiControl

AF:

0.0347

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 08, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

.;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D;D

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.020

.;.;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

N;.;N

REVEL

Benign

0.14

Sift

Benign

0.36

T;.;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0020

.;.;B

Vest4

0.40

MPC

1.1

ClinPred

0.027

GERP RS

5.3

Varity_R

0.18

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over