rs11072514

Variant names:

• chr15-74929524-T-A
• rs11072514
• NM_004255.4:c.101-292A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004255.4(COX5A):​c.101-292A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,100 control chromosomes in the GnomAD database, including 12,226 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 0.35 (12226 hom., cov: 32)
• Consequence: COX5A NM_004255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594
• Publications: 6 publications found

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]

COX5A Gene-Disease associations (from GenCC):

• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex IV deficiency, nuclear type 20

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX5A	NM_004255.4	c.101-292A>T		intron_variant	Intron 1 of 4	ENST00000322347.11	NP_004246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX5A	ENST00000322347.11	c.101-292A>T		intron_variant	Intron 1 of 4	1	NM_004255.4	ENSP00000317780.6

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53585 AN: 151982 Hom.: 12227 Cov.: 32

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.352 AC: 53590 AN: 152100 Hom.: 12226 Cov.: 32 AF XY: 0.341 AC XY: 25343 AN XY: 74346

African (AFR) AF: 0.0969 AC: 4024 AN: 41526

American (AMR) AF: 0.409 AC: 6246 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1373 AN: 3470

East Asian (EAS) AF: 0.112 AC: 582 AN: 5184

South Asian (SAS) AF: 0.122 AC: 588 AN: 4826

European-Finnish (FIN) AF: 0.402 AC: 4252 AN: 10578

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35316 AN: 67946

Other (OTH) AF: 0.360 AC: 761 AN: 2114

Alfa AF: 0.415 Hom.: 1854

Bravo AF: 0.349

Asia WGS AF: 0.120 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.69
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11072514; hg19: chr15-75221865;