14-73958235-T-C

Position:

chr14-73958235-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182476.3(COQ6):c.570T>C(p.His190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,613,646 control chromosomes in the GnomAD database, including 127,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8877 hom., cov: 32)

Exomes 𝑓: 0.39 ( 118799 hom. )

Consequence

COQ6
NM_182476.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0490

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 14-73958235-T-C is Benign according to our data. Variant chr14-73958235-T-C is described in ClinVar as [Benign]. Clinvar id is 128835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73958235-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.049 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ6	NM_182476.3 linkuse as main transcript	c.570T>C	p.His190=	synonymous_variant	5/12	ENST00000334571.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ6	ENST00000334571.7 linkuse as main transcript	c.570T>C	p.His190=	synonymous_variant	5/12	1	NM_182476.3	P1	Q9Y2Z9-1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45949

AN:

152028

Hom.:

8872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0838

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.0451

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.309

GnomAD3 exomes

AF:

0.334

AC:

84090

AN:

251464

Hom.:

16445

AF XY:

0.338

AC XY:

45884

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0771

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.409

Gnomad EAS exome

AF:

0.0322

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.462

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.392

AC:

572598

AN:

1461500

Hom.:

118799

Cov.:

AF XY:

0.388

AC XY:

282334

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.0681

Gnomad4 AMR exome

AF:

0.325

Gnomad4 ASJ exome

AF:

0.410

Gnomad4 EAS exome

AF:

0.0567

Gnomad4 SAS exome

AF:

0.239

Gnomad4 FIN exome

AF:

0.463

Gnomad4 NFE exome

AF:

0.426

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.302

AC:

45954

AN:

152146

Hom.:

8877

Cov.:

AF XY:

0.303

AC XY:

22562

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0835

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.412

Gnomad4 EAS

AF:

0.0452

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.419

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.388

Hom.:

19615

Bravo

AF:

0.281

Asia WGS

AF:

0.182

AC:

634

AN:

3478

EpiCase

AF:

0.409

EpiControl

AF:

0.409

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	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 52% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 48. 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. -
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:3

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

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

-0.50

CADD

Benign

6.3

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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