14-73958353-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0690

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
COQ6	NM_182476.3	c.612+76C>A		intron_variant		ENST00000334571.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ6	ENST00000334571.7	c.612+76C>A		intron_variant		1	NM_182476.3	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61070 AN: 151868 Hom.: 13360 Cov.: 32

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

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.: 37 AF XY: 0.472 AC XY: 341254 AN XY: 722658

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.: 32 AF XY: 0.407 AC XY: 30213 AN XY: 74250

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs3764859; hg19: chr14-74425056; COSMIC: COSV53178887; COSMIC: COSV53178887;