dbSNP rs1130569: COX6C:p.Tyr56Tyr (chr8-99887565-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004374.4(COX6C):c.168C>T(p.Tyr56Tyr) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Variant links:

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]

COX6C links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
COX6C	NM_004374.4 link	c.168C>T	p.Tyr56Tyr	synonymous_variant	Exon 3 of 4	ENST00000520468.7	NP_004365.1	P09669A0A024R9B7
COX6C	XM_017013020.2 link	c.168C>T	p.Tyr56Tyr	synonymous_variant	Exon 3 of 4		XP_016868509.1	P09669A0A024R9B7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX6C	ENST00000520468.7 link	c.168C>T	p.Tyr56Tyr	synonymous_variant	Exon 3 of 4	1	NM_004374.4	ENSP00000428895.1		P09669

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39496

AN:

151810

Hom.:

6740

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.179

AC XY:

129841

AN XY:

724000

show subpopulations

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.:

AF XY:

0.255

AC XY:

18973

AN XY:

74260

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over