17-14069638-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001303.4(COX10):c.33C>T(p.Arg11Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,613,798 control chromosomes in the GnomAD database, including 3,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 291 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3708 hom. )

Consequence

COX10
NM_001303.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.20

Publications

9 publications found

Variant links:

Genes affected

COX10 (HGNC:2260): (cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10) Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes heme A:farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. This protein is predicted to contain 7-9 transmembrane domains localized in the mitochondrial inner membrane. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion. [provided by RefSeq, Jul 2008]

COX10 links:

COX10-DT (HGNC:38873): (COX10 divergent transcript)

COX10-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 17-14069638-C-T is Benign according to our data. Variant chr17-14069638-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX10	NM_001303.4	MANE Select	c.33C>T	p.Arg11Arg	synonymous	Exon 1 of 7	NP_001294.2
	COX10-DT	NR_049718.1		n.-180G>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COX10	ENST00000261643.8	TSL:1 MANE Select	c.33C>T	p.Arg11Arg	synonymous	Exon 1 of 7	ENSP00000261643.3	Q12887-1
COX10	ENST00000886734.1		c.33C>T	p.Arg11Arg	synonymous	Exon 1 of 6	ENSP00000556793.1
COX10	ENST00000886735.1		c.33C>T	p.Arg11Arg	synonymous	Exon 1 of 5	ENSP00000556794.1

Frequencies

GnomAD3 genomes

AF:

0.0542

AC:

8242

AN:

152168

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0434

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.0280

Gnomad SAS

AF:

0.0373

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0747

Gnomad OTH

AF:

0.0546

GnomAD2 exomes

AF:

0.0589

AC:

14639

AN:

248538

AF XY:

0.0602

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0572

Gnomad EAS exome

AF:

0.0308

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.0715

Gnomad OTH exome

AF:

0.0639

GnomAD4 exome

AF:

0.0675

AC:

98720

AN:

1461512

Hom.:

3708

Cov.:

AF XY:

0.0670

AC XY:

48693

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.00917

AC:

307

AN:

33478

American (AMR)

AF:

0.0289

AC:

1294

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

1542

AN:

26122

East Asian (EAS)

AF:

0.0258

AC:

1025

AN:

39696

South Asian (SAS)

AF:

0.0405

AC:

3490

AN:

86232

European-Finnish (FIN)

AF:

0.133

AC:

7119

AN:

53352

Middle Eastern (MID)

AF:

0.0322

AC:

186

AN:

5768

European-Non Finnish (NFE)

AF:

0.0720

AC:

79995

AN:

1111768

Other (OTH)

AF:

0.0623

AC:

3762

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

4960

9920

14880

19840

24800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2882

5764

8646

11528

14410

<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:

0.0541

AC:

8240

AN:

152286

Hom.:

291

Cov.:

AF XY:

0.0557

AC XY:

4148

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0118

AC:

489

AN:

41582

American (AMR)

AF:

0.0434

AC:

664

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0542

AC:

188

AN:

3470

East Asian (EAS)

AF:

0.0279

AC:

144

AN:

5162

South Asian (SAS)

AF:

0.0371

AC:

179

AN:

4828

European-Finnish (FIN)

AF:

0.129

AC:

1365

AN:

10604

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0747

AC:

5083

AN:

68012

Other (OTH)

AF:

0.0540

AC:

114

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

408

815

1223

1630

2038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0615

Hom.:

498

Bravo

AF:

0.0448

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.0668

EpiControl

AF:

0.0665

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Leigh syndrome (1)

Mitochondrial complex IV deficiency, nuclear type 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

1.2

PromoterAI

0.060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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