Genetic Variant COQ6:n.88+113G>T (chr14-73950293-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182480.3(COQ6):c.88+113G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,541,696 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 142 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 151 hom. )

Consequence

COQ6
NM_182480.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.389

Publications

3 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:

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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=-0.72).

BP6

Variant 14-73950293-G-T is Benign according to our data. Variant chr14-73950293-G-T is described in ClinVar as Benign. ClinVar VariationId is 136987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0821 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	Effect	Exon Rank	Protein	UniProt
COQ6	NM_182480.3	c.88+113G>T	intron	N/A	NP_872286.2	Q9Y2Z9-3
COQ6	NM_001425258.1	c.88+113G>T	intron	N/A	NP_001412187.1
COQ6	NM_001425259.1	c.-4+113G>T	intron	N/A	NP_001412188.1	A0A0D9SFJ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COQ6	ENST00000554341.6	TSL:1	n.88+113G>T	intron	N/A	ENSP00000450736.2	G3V2L5
FAM161B	ENST00000651776.1		c.-78C>A	5_prime_UTR	Exon 1 of 9	ENSP00000499021.1	Q96MY7-2
COQ6	ENST00000963229.1		c.-40G>T	5_prime_UTR	Exon 1 of 12	ENSP00000633288.1

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3702

AN:

152270

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00863

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0186

GnomAD2 exomes

AF:

0.00619

AC:

907

AN:

146580

AF XY:

0.00455

show subpopulations

Gnomad AFR exome

AF:

0.0984

Gnomad AMR exome

AF:

0.00404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000455

Gnomad OTH exome

AF:

0.00325

GnomAD4 exome

AF:

0.00258

AC:

3584

AN:

1389310

Hom.:

151

Cov.:

AF XY:

0.00221

AC XY:

1515

AN XY:

685986

show subpopulations

African (AFR)

AF:

0.0912

AC:

2893

AN:

31710

American (AMR)

AF:

0.00463

AC:

166

AN:

35828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25190

East Asian (EAS)

AF:

0.00

AC:

AN:

35866

South Asian (SAS)

AF:

0.0000755

AC:

AN:

79520

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37778

Middle Eastern (MID)

AF:

0.00421

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.000174

AC:

188

AN:

1079718

Other (OTH)

AF:

0.00529

AC:

307

AN:

58002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

266

531

797

1062

1328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.0243

AC:

3709

AN:

152386

Hom.:

142

Cov.:

AF XY:

0.0225

AC XY:

1673

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.0844

AC:

3510

AN:

41590

American (AMR)

AF:

0.00862

AC:

132

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000367

AC:

AN:

68044

Other (OTH)

AF:

0.0184

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

190

380

569

759

949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0105

Hom.:

Bravo

AF:

0.0282

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.6

(source)

DANN

Benign

0.77

PhyloP100

-0.39

PromoterAI

-0.17

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over