chr14-73950133-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBA1

The NM_182480.3(COQ6):c.41G>A(p.Trp14*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,598,314 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 63 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 73 hom. )

Consequence

COQ6
NM_182480.3 stop_gained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.97

Publications

15 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 links:

FAM161B (HGNC:19854): (FAM161 centrosomal protein B) Predicted to be involved in cilium organization. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

FAM161B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 25 pathogenic variants in the truncated region.

BP6

Variant 14-73950133-G-A is Benign according to our data. Variant chr14-73950133-G-A is described in ClinVar as Benign. ClinVar VariationId is 136986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182480.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ6	NM_182480.3	c.41G>A	p.Trp14*	stop_gained	Exon 1 of 12	NP_872286.2	Q9Y2Z9-3
COQ6	NM_001425258.1	c.41G>A	p.Trp14*	stop_gained	Exon 1 of 11	NP_001412187.1
COQ6	NM_001425259.1	c.-51G>A		5_prime_UTR	Exon 1 of 11	NP_001412188.1	A0A0D9SFJ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ6	ENST00000554341.6	TSL:1	n.41G>A		non_coding_transcript_exon	Exon 1 of 11	ENSP00000450736.2	G3V2L5
COQ6	ENST00000394026.8	TSL:2	c.41G>A	p.Trp14*	stop_gained	Exon 1 of 12	ENSP00000377594.4	Q9Y2Z9-3
FAM161B	ENST00000651776.1		c.83C>T	p.Pro28Leu	missense	Exon 1 of 9	ENSP00000499021.1	Q96MY7-2

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2354

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0119

GnomAD2 exomes

AF:

0.00402

AC:

904

AN:

224968

AF XY:

0.00316

show subpopulations

Gnomad AFR exome

AF:

0.0555

Gnomad AMR exome

AF:

0.00302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000172

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000319

Gnomad OTH exome

AF:

0.00211

GnomAD4 exome

AF:

0.00183

AC:

2646

AN:

1445954

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1181

AN XY:

719758

show subpopulations

African (AFR)

AF:

0.0567

AC:

1892

AN:

33372

American (AMR)

AF:

0.00334

AC:

148

AN:

44248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.000329

AC:

AN:

39546

South Asian (SAS)

AF:

0.000105

AC:

AN:

86078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39730

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000278

AC:

309

AN:

1111012

Other (OTH)

AF:

0.00426

AC:

256

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

223

446

670

893

1116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.0155

AC:

2363

AN:

152360

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1090

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.0534

AC:

2219

AN:

41578

American (AMR)

AF:

0.00523

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68040

Other (OTH)

AF:

0.0118

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

118

236

355

473

591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0154

Hom.:

Bravo

AF:

0.0176

ExAC

AF:

0.00471

AC:

568

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

COQ6-related disorder (1)

Familial steroid-resistant nephrotic syndrome with sensorineural deafness (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.2

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

PhyloP100

2.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.46

REVEL

Benign

0.020

Sift

Uncertain

0.015

Vest4

0.16

MVP

0.27

MPC

0.065

ClinPred

0.048

GERP RS

3.3

PromoterAI

-0.0024

Neutral

(source)

Mutation Taster

=127/73

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over