Genetic Variant NM_182476.3:c.570T>C (chr14-73958235-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182476.3(COQ6):c.570T>C(p.His190His) 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

Publications

26 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:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 128835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182476.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ6	NM_182476.3	MANE Select	c.570T>C	p.His190His	synonymous	Exon 5 of 12	NP_872282.1	Q9Y2Z9-1
COQ6	NM_001425255.1		c.570T>C	p.His190His	synonymous	Exon 5 of 11	NP_001412184.1
COQ6	NM_182480.3		c.495T>C	p.His165His	synonymous	Exon 5 of 12	NP_872286.2	Q9Y2Z9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ6	ENST00000334571.7	TSL:1 MANE Select	c.570T>C	p.His190His	synonymous	Exon 5 of 12	ENSP00000333946.2	Q9Y2Z9-1
COQ6	ENST00000554341.6	TSL:1	n.*175T>C		non_coding_transcript_exon	Exon 4 of 11	ENSP00000450736.2	G3V2L5
COQ6	ENST00000556300.6	TSL:1	n.604T>C		non_coding_transcript_exon	Exon 5 of 5

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

GnomAD2 exomes

AF:

0.334

AC:

84090

AN:

251464

AF XY:

0.338

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 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

African (AFR)

AF:

0.0681

AC:

2280

AN:

33476

American (AMR)

AF:

0.325

AC:

14523

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

10722

AN:

26132

East Asian (EAS)

AF:

0.0567

AC:

2250

AN:

39690

South Asian (SAS)

AF:

0.239

AC:

20624

AN:

86250

European-Finnish (FIN)

AF:

0.463

AC:

24713

AN:

53398

Middle Eastern (MID)

AF:

0.318

AC:

1831

AN:

5766

European-Non Finnish (NFE)

AF:

0.426

AC:

473587

AN:

1111698

Other (OTH)

AF:

0.366

AC:

22068

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

18932

37864

56796

75728

94660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13990

27980

41970

55960

69950

<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:

0.302

AC:

45954

AN:

152146

Hom.:

8877

Cov.:

AF XY:

0.303

AC XY:

22562

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0835

AC:

3473

AN:

41576

American (AMR)

AF:

0.337

AC:

5154

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

1429

AN:

3468

East Asian (EAS)

AF:

0.0452

AC:

234

AN:

5176

South Asian (SAS)

AF:

0.227

AC:

1093

AN:

4818

European-Finnish (FIN)

AF:

0.473

AC:

4984

AN:

10542

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.419

AC:

28502

AN:

67982

Other (OTH)

AF:

0.312

AC:

658

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1445

2890

4335

5780

7225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.380

Hom.:

23145

Bravo

AF:

0.281

Asia WGS

AF:

0.182

AC:

634

AN:

3478

EpiCase

AF:

0.409

EpiControl

AF:

0.409

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.3

(source)

DANN

Benign

0.74

PhyloP100

0.049

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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