11-63974702-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004074.3(COX8A):c.22C>T(p.Leu8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00643 in 1,609,600 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 154 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 159 hom. )

Consequence

COX8A
NM_004074.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.16

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 11-63974702-C-T is Benign according to our data. Variant chr11-63974702-C-T is described in ClinVar as [Benign]. Clinvar id is 673121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX8A	NM_004074.3 linkuse as main transcript	c.22C>T	p.Leu8=	synonymous_variant	1/2	ENST00000314133.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX8A	ENST00000314133.4 linkuse as main transcript	c.22C>T	p.Leu8=	synonymous_variant	1/2	1	NM_004074.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4033

AN:

152254

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0838

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.0454

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0113

AC:

2710

AN:

239998

Hom.:

AF XY:

0.00928

AC XY:

1210

AN XY:

130340

show subpopulations

Gnomad AFR exome

AF:

0.0873

Gnomad AMR exome

AF:

0.00619

Gnomad ASJ exome

AF:

0.00379

Gnomad EAS exome

AF:

0.0536

Gnomad SAS exome

AF:

0.00396

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000444

Gnomad OTH exome

AF:

0.00480

GnomAD4 exome

AF:

0.00433

AC:

6316

AN:

1457228

Hom.:

159

Cov.:

AF XY:

0.00402

AC XY:

2914

AN XY:

724552

show subpopulations

Gnomad4 AFR exome

AF:

0.0842

Gnomad4 AMR exome

AF:

0.00629

Gnomad4 ASJ exome

AF:

0.00324

Gnomad4 EAS exome

AF:

0.0464

Gnomad4 SAS exome

AF:

0.00370

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000295

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.0265

AC:

4038

AN:

152372

Hom.:

154

Cov.:

AF XY:

0.0258

AC XY:

1919

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0836

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.0455

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00611

Hom.:

Bravo

AF:

0.0312

Asia WGS

AF:

0.0290

AC:

103

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -

COX8A-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 06, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Benign

0.91

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over