Variant 14-73958353-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182476.3(COQ6):c.612+76C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,604,650 control chromosomes in the GnomAD database, including 176,855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13351 hom., cov: 32)

Exomes 𝑓: 0.47 ( 163504 hom. )

Consequence

COQ6
NM_182476.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0690

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:

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 (BayesDel_noAF=-0.89).

BP6

Variant 14-73958353-C-A is Benign according to our data. Variant chr14-73958353-C-A is described in ClinVar as [Benign]. Clinvar id is 1250141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73958353-C-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.612+76C>A		intron_variant		ENST00000334571.7	NP_872282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ6	ENST00000334571.7 linkuse as main transcript	c.612+76C>A		intron_variant		1	NM_182476.3	ENSP00000333946	P1	Q9Y2Z9-1

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61070

AN:

151868

Hom.:

13360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.547

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.422

GnomAD3 exomes

AF:

0.441

AC:

108394

AN:

245912

Hom.:

25191

AF XY:

0.452

AC XY:

60117

AN XY:

133078

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.493

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.504

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.482

Gnomad OTH exome

AF:

0.470

GnomAD4 exome

AF:

0.470

AC:

682542

AN:

1452666

Hom.:

163504

Cov.:

AF XY:

0.472

AC XY:

341254

AN XY:

722658

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.406

Gnomad4 ASJ exome

AF:

0.498

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.505

Gnomad4 FIN exome

AF:

0.538

Gnomad4 NFE exome

AF:

0.482

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.402

AC:

61072

AN:

151984

Hom.:

13351

Cov.:

AF XY:

0.407

AC XY:

30213

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.440

Gnomad4 ASJ

AF:

0.497

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.495

Gnomad4 FIN

AF:

0.547

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.424

Alfa

AF:

0.391

Hom.:

2851

Bravo

AF:

0.380

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.93

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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