rs8500

Positions:

chr14-73961742-G-A

Variant summary

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

The NM_182476.3(COQ6):c.1216G>A(p.Val406Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,613,496 control chromosomes in the GnomAD database, including 177,834 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13309 hom., cov: 31)

Exomes 𝑓: 0.47 ( 164525 hom. )

Consequence

COQ6
NM_182476.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.04

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=8.6542964E-4).

BP6

Variant 14-73961742-G-A is Benign according to our data. Variant chr14-73961742-G-A is described in ClinVar as [Benign]. Clinvar id is 128834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73961742-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 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.1216G>A	p.Val406Met	missense_variant	11/12	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.1216G>A	p.Val406Met	missense_variant	11/12	1	NM_182476.3	ENSP00000333946.2		Q9Y2Z9-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60761

AN:

151870

Hom.:

13317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.547

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.421

GnomAD3 exomes

AF:

0.439

AC:

110366

AN:

251462

Hom.:

25798

AF XY:

0.450

AC XY:

61152

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.188

Gnomad SAS exome

AF:

0.504

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.481

Gnomad OTH exome

AF:

0.469

GnomAD4 exome

AF:

0.470

AC:

686380

AN:

1461508

Hom.:

164525

Cov.:

AF XY:

0.472

AC XY:

343231

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.498

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.504

Gnomad4 FIN exome

AF:

0.538

Gnomad4 NFE exome

AF:

0.482

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.400

AC:

60765

AN:

151988

Hom.:

13309

Cov.:

AF XY:

0.405

AC XY:

30062

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.222

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.497

Gnomad4 EAS

AF:

0.208

Gnomad4 SAS

AF:

0.495

Gnomad4 FIN

AF:

0.547

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.423

Alfa

AF:

0.462

Hom.:

43116

Bravo

AF:

0.378

TwinsUK

AF:

0.473

AC:

1754

ALSPAC

AF:

0.479

AC:

1845

ESP6500AA

AF:

0.213

AC:

940

ESP6500EA

AF:

0.472

AC:

4061

ExAC

AF:

0.435

AC:

52763

Asia WGS

AF:

0.389

AC:

1354

AN:

3478

EpiCase

AF:

0.482

EpiControl

AF:

0.485

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 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. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 58% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 54. Only high quality variants are reported. -
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. -

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 19, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Familial steroid-resistant nephrotic syndrome with sensorineural deafness

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.065

.;T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.32

T;T;T

MetaRNN

Benign

0.00087

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.56

.;.;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.15

N;.;N

REVEL

Benign

0.070

Sift

Benign

0.55

T;.;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.0030

.;.;B

Vest4

0.089

MPC

0.29

ClinPred

0.0059

GERP RS

4.1

Varity_R

0.041

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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