14-73953424-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

familial steroid-resistant nephrotic syndrome with sensorineural deafness
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
SMARCB1-related schwannomatosis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

COQ6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 136983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ6	NM_182476.3 link	c.164-11C>T		intron_variant	Intron 1 of 11	ENST00000334571.7	NP_872282.1	Q9Y2Z9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ6	ENST00000334571.7 link	c.164-11C>T		intron_variant	Intron 1 of 11	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

GnomAD2 exomes

AF:

0.233

AC:

57159

AN:

245772

AF XY:

0.226

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 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

African (AFR)

AF:

0.305

AC:

9890

AN:

32476

American (AMR)

AF:

0.335

AC:

14580

AN:

43488

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

4528

AN:

25930

East Asian (EAS)

AF:

0.378

AC:

14773

AN:

39124

South Asian (SAS)

AF:

0.252

AC:

21325

AN:

84734

European-Finnish (FIN)

AF:

0.165

AC:

8789

AN:

53254

Middle Eastern (MID)

AF:

0.150

AC:

851

AN:

5686

European-Non Finnish (NFE)

AF:

0.188

AC:

205915

AN:

1093796

Other (OTH)

AF:

0.207

AC:

12291

AN:

59448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

10987

21974

32961

43948

54935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7602

15204

22806

30408

38010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.239

AC:

36368

AN:

151968

Hom.:

4676

Cov.:

AF XY:

0.238

AC XY:

17695

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.314

AC:

13010

AN:

41444

American (AMR)

AF:

0.256

AC:

3907

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

659

AN:

3466

East Asian (EAS)

AF:

0.397

AC:

2054

AN:

5172

South Asian (SAS)

AF:

0.273

AC:

1312

AN:

4812

European-Finnish (FIN)

AF:

0.157

AC:

1660

AN:

10562

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.192

AC:

13062

AN:

67960

Other (OTH)

AF:

0.212

AC:

447

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1321

2642

3962

5283

6604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

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 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. -

Sep 19, 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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.21

(source)

DANN

Benign

0.55

PhyloP100

-0.58

Mutation Taster

=52/48

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over