rs8903

chr12-120440727-T-Cchr12-120440727-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_004373.4(COX6A1):c.*190T>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 0.693 in 504,762 control chromosomes in the GnomAD database, including 123,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (41682 hom., cov: 33)
  • Exomes 𝑓: 0.68 (81473 hom.)
• Consequence: COX6A1 NM_004373.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970

Genes affected

COX6A1 (HGNC:2277): (cytochrome c oxidase subunit 6A1) Cytochrome c oxidase (COX), 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 the electron transfer and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes polypeptide 1 (liver isoform) of subunit VIa, and polypeptide 1 is found in all non-muscle tissues. Polypeptide 2 (heart/muscle isoform) of subunit VIa is encoded by a different gene, and is present only in striated muscles. These two polypeptides share 66% amino acid sequence identity. It has been reported that there may be several pseudogenes on chromosomes 1, 6, 7q21, 7q31-32 and 12. However, only one pseudogene (COX6A1P) on chromosome 1p31.1 has been documented. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 12-120440727-T-C is Benign according to our data. Variant chr12-120440727-T-C is described in ClinVar as [Benign]. Clinvar id is 1235763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX6A1	NM_004373.4	c.*190T>C		3_prime_UTR_variant	3/3	ENST00000229379.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX6A1	ENST00000229379.3	c.*190T>C		3_prime_UTR_variant	3/3	1	NM_004373.4	P1
COX6A1	ENST00000549525.1	n.757T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110910 AN: 152030 Hom.: 41624 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.666

GnomAD4 exome AF: 0.676 AC: 238528 AN: 352614 Hom.: 81473 Cov.: 4 AF XY: 0.676 AC XY: 124056 AN XY: 183494

Gnomad4 AFR exome AF: 0.909

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.705

Gnomad4 SAS exome AF: 0.683

Gnomad4 FIN exome AF: 0.698

Gnomad4 NFE exome AF: 0.661

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.730 AC: 111026 AN: 152148 Hom.: 41682 Cov.: 33 AF XY: 0.729 AC XY: 54243 AN XY: 74366

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.660

Alfa AF: 0.652 Hom.: 10446

Bravo AF: 0.729

Asia WGS AF: 0.707 AC: 2460 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	13
Dann	Benign	0.85

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: rs8903; hg19: chr12-120878530; COSMIC: COSV56663721; COSMIC: COSV56663721;