rs8042694

Positions:

• chr15-74933074-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000322347.11(COX5A):​c.101-3842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,884 control chromosomes in the GnomAD database, including 36,275 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36275 hom., cov: 30)
• Consequence: COX5A ENST00000322347.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

Genes affected

COX5A (HGNC:2267): (cytochrome c oxidase subunit 5A) Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane. The complex consists of 13 mitochondrial- and nuclear-encoded subunits. The mitochondrially-encoded subunits perform the electron transfer of proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex. This gene encodes the nuclear-encoded subunit Va of the human mitochondrial respiratory chain enzyme. A pseudogene COX5AP1 has been found in chromosome 14q22. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX5A	NM_004255.4	c.101-3842C>T		intron_variant		ENST00000322347.11	NP_004246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX5A	ENST00000322347.11	c.101-3842C>T		intron_variant		1	NM_004255.4	ENSP00000317780	P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104652 AN: 151766 Hom.: 36239 Cov.: 30

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.693

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.690 AC: 104737 AN: 151884 Hom.: 36275 Cov.: 30 AF XY: 0.686 AC XY: 50949 AN XY: 74230

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.694

Alfa AF: 0.687 Hom.: 19404

Bravo AF: 0.701

Asia WGS AF: 0.802 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs8042694; hg19: chr15-75225415;