rs61759492

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004074.3(COX8A):c.111C>A(p.Ile37Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,601,624 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 39 hom. )

Consequence

COX8A
NM_004074.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.643

Publications

6 publications found

Variant links:

Genes affected

COX8A (HGNC:2294): (cytochrome c oxidase subunit 8A) The protein encoded by this gene is the terminal enzyme of the respiratory chain, coupling the transfer of electrons from cytochrome c to molecular oxygen, with the concomitant production of a proton electrochemical gradient across the inner mitochondrial membrane. In addition to 3 mitochondrially encoded subunits, which perform the catalytic function, the eukaryotic enzyme contains nuclear-encoded smaller subunits, ranging in number from 4 in some organisms to 10 in mammals. It has been proposed that nuclear-encoded subunits may be involved in the modulation of the catalytic function. This gene encodes one of the nuclear-encoded subunits. [provided by RefSeq, Jul 2008]

COX8A Gene-Disease associations (from GenCC):

cytochrome-c oxidase deficiency disease
Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
mitochondrial complex IV deficiency, nuclear type 15
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
mitochondrial disease
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

COX8A links:

ENSG00000256100 (HGNC:):

ENSG00000256100 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 11-63974791-C-A is Benign according to our data. Variant chr11-63974791-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 709505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.643 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004074.3. 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
	COX8A	NM_004074.3	MANE Select	c.111C>A	p.Ile37Ile	synonymous	Exon 1 of 2	NP_004065.1	P10176

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX8A	ENST00000314133.4	TSL:1 MANE Select	c.111C>A	p.Ile37Ile	synonymous	Exon 1 of 2	ENSP00000321260.3	P10176
	ENSG00000256100	ENST00000535431.1	TSL:5	n.172C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00499

AC:

759

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00760

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00480

AC:

1073

AN:

223360

AF XY:

0.00491

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.00270

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.0000582

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00753

Gnomad OTH exome

AF:

0.00427

GnomAD4 exome

AF:

0.00730

AC:

10586

AN:

1449262

Hom.:

Cov.:

AF XY:

0.00715

AC XY:

5152

AN XY:

720078

show subpopulations

African (AFR)

AF:

0.000930

AC:

AN:

33322

American (AMR)

AF:

0.00245

AC:

105

AN:

42808

Ashkenazi Jewish (ASJ)

AF:

0.0000780

AC:

AN:

25630

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39384

South Asian (SAS)

AF:

0.000272

AC:

AN:

84598

European-Finnish (FIN)

AF:

0.0101

AC:

527

AN:

52294

Middle Eastern (MID)

AF:

0.00320

AC:

AN:

5618

European-Non Finnish (NFE)

AF:

0.00862

AC:

9531

AN:

1105798

Other (OTH)

AF:

0.00582

AC:

348

AN:

59810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

523

1047

1570

2094

2617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.00497

AC:

757

AN:

152362

Hom.:

Cov.:

AF XY:

0.00502

AC XY:

374

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41598

American (AMR)

AF:

0.00399

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0102

AC:

108

AN:

10624

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00760

AC:

517

AN:

68042

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00412

Hom.:

Bravo

AF:

0.00449

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Mitochondrial complex IV deficiency, nuclear type 15 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.9

(source)

DANN

Benign

0.63

PhyloP100

0.64

PromoterAI

-0.071

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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