14-73953424-C-T

Position:

chr14-73953424-C-T

Variant summary

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

The NM_182476.3(COQ6):c.164-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,589,904 control chromosomes in the GnomAD database, including 32,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4676 hom., cov: 32)

Exomes 𝑓: 0.20 ( 27874 hom. )

Consequence

COQ6
NM_182476.3 intron

Scores

Splicing: ADA: 0.00001369

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.578

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:

COQ6 (HGNC:):

COQ6 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 14-73953424-C-T is Benign according to our data. Variant chr14-73953424-C-T is described in ClinVar as [Benign]. Clinvar id is 136983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73953424-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 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.164-11C>T		intron_variant		ENST00000334571.7	NP_872282.1	Q9Y2Z9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ6	ENST00000334571.7 linkuse as main transcript	c.164-11C>T		intron_variant		1	NM_182476.3	ENSP00000333946.2		Q9Y2Z9-1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36317

AN:

151854

Hom.:

4666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.233

AC:

57159

AN:

245772

Hom.:

6312

AF XY:

0.226

AC XY:

30065

AN XY:

133314

show subpopulations

Gnomad AFR exome

AF:

0.303

Gnomad AMR exome

AF:

0.335

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.388

Gnomad SAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.204

AC:

292942

AN:

1437936

Hom.:

27874

Cov.:

AF XY:

0.204

AC XY:

145976

AN XY:

716320

show subpopulations

Gnomad4 AFR exome

AF:

0.305

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.175

Gnomad4 EAS exome

AF:

0.378

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.239

AC:

36368

AN:

151968

Hom.:

4676

Cov.:

AF XY:

0.238

AC XY:

17695

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.0759

Hom.:

211

Bravo

AF:

0.256

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 45% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 42. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 19, 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:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.21

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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