14-73961583-A-G

Variant names:

• chr14-73961583-A-G
• rs7141392
• NM_182476.3:c.1210+13A>G

Variant summary

Our verdict is Benign. The variant received -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:5
• Conservation: PhyloP100: 0.759
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 136982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
COQ6	NM_182476.3	c.1210+13A>G		intron_variant	Intron 10 of 11	ENST00000334571.7	NP_872282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ6	ENST00000334571.7	c.1210+13A>G		intron_variant	Intron 10 of 11	1	NM_182476.3	ENSP00000333946.2

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

GnomAD2 exomes AF: 0.884 AC: 221798 AN: 251004 AF XY: 0.885

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 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

African (AFR) AF: 0.768 AC: 25702 AN: 33466

American (AMR) AF: 0.898 AC: 40122 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 21965 AN: 26128

East Asian (EAS) AF: 0.953 AC: 37840 AN: 39696

South Asian (SAS) AF: 0.919 AC: 79298 AN: 86242

European-Finnish (FIN) AF: 0.908 AC: 48497 AN: 53404

Middle Eastern (MID) AF: 0.846 AC: 4879 AN: 5768

European-Non Finnish (NFE) AF: 0.879 AC: 976847 AN: 1111468

Other (OTH) AF: 0.872 AC: 52673 AN: 60376

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

African (AFR) AF: 0.771 AC: 31976 AN: 41488

American (AMR) AF: 0.846 AC: 12925 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2920 AN: 3468

East Asian (EAS) AF: 0.945 AC: 4886 AN: 5170

South Asian (SAS) AF: 0.921 AC: 4447 AN: 4828

European-Finnish (FIN) AF: 0.914 AC: 9682 AN: 10592

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59390 AN: 68024

Other (OTH) AF: 0.839 AC: 1773 AN: 2114

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Sep 05, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial steroid-resistant nephrotic syndrome with sensorineural deafness Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	17
DANN	Benign	0.54
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7141392; hg19: chr14-74428286;