15-74920016-A-G

Variant summary

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

The NM_004255.4(COX5A):c.*436T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 254,372 control chromosomes in the GnomAD database, including 25,874 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 0.37 (13524 hom., cov: 32)
  • Exomes 𝑓: 0.47 (12350 hom.)
• Consequence: COX5A NM_004255.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX5A	NM_004255.4	c.*436T>C		3_prime_UTR_variant	5/5	ENST00000322347.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX5A	ENST00000322347.11	c.*436T>C		3_prime_UTR_variant	5/5	1	NM_004255.4	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56918 AN: 151956 Hom.: 13524 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.465 AC: 47581 AN: 102298 Hom.: 12350 Cov.: 0 AF XY: 0.445 AC XY: 23778 AN XY: 53426

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.468

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.439

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.374 AC: 56924 AN: 152074 Hom.: 13524 Cov.: 32 AF XY: 0.365 AC XY: 27138 AN XY: 74350

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.392

Alfa AF: 0.500 Hom.: 34174

Bravo AF: 0.371

Asia WGS AF: 0.178 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	11
Dann	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1133322; hg19: chr15-75212357; COSMIC: COSV59279977; COSMIC: COSV59279977;