14-73961583-A-G

Position:

• chr14-73961583-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_182476.3(COQ6):​c.1210+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 1,613,424 control chromosomes in the GnomAD database, including 623,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55037 hom., cov: 32)
  • Exomes 𝑓: 0.88 (568219 hom.)
• Consequence: COQ6 NM_182476.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.759

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 -16 ACMG points.

• BP6: Variant 14-73961583-A-G is Benign according to our data. Variant chr14-73961583-A-G is described in ClinVar as [Benign]. Clinvar id is 136982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73961583-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ6	NM_182476.3	c.1210+13A>G		intron_variant		ENST00000334571.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ6	ENST00000334571.7	c.1210+13A>G		intron_variant		1	NM_182476.3	P1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 129005 AN: 152058 Hom.: 54993 Cov.: 32

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.838

GnomAD3 exomes AF: 0.884 AC: 221798 AN: 251004 Hom.: 98291 AF XY: 0.885 AC XY: 120100 AN XY: 135662

Gnomad AFR exome AF: 0.770

Gnomad AMR exome AF: 0.903

Gnomad ASJ exome AF: 0.838

Gnomad EAS exome AF: 0.944

Gnomad SAS exome AF: 0.921

Gnomad FIN exome AF: 0.911

Gnomad NFE exome AF: 0.874

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.881 AC: 1287823 AN: 1461248 Hom.: 568219 Cov.: 39 AF XY: 0.882 AC XY: 641214 AN XY: 726924

Gnomad4 AFR exome AF: 0.768

Gnomad4 AMR exome AF: 0.898

Gnomad4 ASJ exome AF: 0.841

Gnomad4 EAS exome AF: 0.953

Gnomad4 SAS exome AF: 0.919

Gnomad4 FIN exome AF: 0.908

Gnomad4 NFE exome AF: 0.879

Gnomad4 OTH exome AF: 0.872

GnomAD4 genome AF: 0.848 AC: 129104 AN: 152176 Hom.: 55037 Cov.: 32 AF XY: 0.851 AC XY: 63308 AN XY: 74388

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.921

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.839

Alfa AF: 0.859 Hom.: 11544

Bravo AF: 0.842

Asia WGS AF: 0.911 AC: 3168 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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 96% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 89. Only high quality variants are reported. -
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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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
BayesDel_noAF	Benign	-0.93
CADD	Benign	17
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs7141392; hg19: chr14-74428286;