rs1133323

Positions:

• chr15-74919884-C-T

Variant summary

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

The NM_004255.4(COX5A):​c.*568G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 153,274 control chromosomes in the GnomAD database, including 12,332 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 (12213 hom., cov: 32)
  • Exomes 𝑓: 0.40 (119 hom.)
• Consequence: COX5A NM_004255.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

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=-0.68).
• 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/exons	MANE	UniProt
COX5A	NM_004255.4	c.*568G>A		3_prime_UTR_variant	5/5	ENST00000322347.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX5A	ENST00000322347.11	c.*568G>A		3_prime_UTR_variant	5/5	1	NM_004255.4	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53546 AN: 151916 Hom.: 12214 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.402 AC: 499 AN: 1240 Hom.: 119 Cov.: 0 AF XY: 0.378 AC XY: 253 AN XY: 670

Gnomad4 AFR exome AF: 0.0833

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.476

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.379

GnomAD4 genome AF: 0.352 AC: 53551 AN: 152034 Hom.: 12213 Cov.: 32 AF XY: 0.341 AC XY: 25316 AN XY: 74298

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.359

Alfa AF: 0.470 Hom.: 18005

Bravo AF: 0.349

Asia WGS AF: 0.121 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.5
DANN	Benign	0.84

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: rs1133323; hg19: chr15-75212225;