rs1130569

Positions:

• chr8-99887565-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004374.4(COX6C):​c.168C>T​(p.Tyr56=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,607,334 control chromosomes in the GnomAD database, including 33,408 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 0.26 (6758 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26650 hom.)
• Consequence: COX6C NM_004374.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

Genes affected

COX6C (HGNC:2285): (cytochrome c oxidase subunit 6C) Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIc, which has 77% amino acid sequence identity with mouse subunit VIc. This gene is up-regulated in prostate cancer cells. A pseudogene has been found on chromosomes 16p12. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=1.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX6C	NM_004374.4	c.168C>T	p.Tyr56=	synonymous_variant	3/4	ENST00000520468.7
COX6C	XM_017013020.2	c.168C>T	p.Tyr56=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX6C	ENST00000520468.7	c.168C>T	p.Tyr56=	synonymous_variant	3/4	1	NM_004374.4	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39496 AN: 151810 Hom.: 6740 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.214

GnomAD3 exomes AF: 0.183 AC: 45194 AN: 246822 Hom.: 5103 AF XY: 0.176 AC XY: 23540 AN XY: 133544

Gnomad AFR exome AF: 0.490

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.126

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.182 AC: 264492 AN: 1455406 Hom.: 26650 Cov.: 30 AF XY: 0.179 AC XY: 129841 AN XY: 724000

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.260 AC: 39550 AN: 151928 Hom.: 6758 Cov.: 32 AF XY: 0.255 AC XY: 18973 AN XY: 74260

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.211

Alfa AF: 0.219 Hom.: 2593

Bravo AF: 0.275

Asia WGS AF: 0.166 AC: 579 AN: 3478

EpiCase AF: 0.182

EpiControl AF: 0.179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.8
DANN	Benign	0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1130569; hg19: chr8-100899793; COSMIC: COSV52553411;