Variant rs8903 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0970

Variant links:

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]

COX6A1 links:

ENSG00000111780 (HGNC:):

ENSG00000111780 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
COX6A1	NM_004373.4 linkuse as main transcript	c.*190T>C		3_prime_UTR_variant	3/3	ENST00000229379.3	NP_004364.2	P12074H6SG15

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COX6A1	ENST00000229379.3 linkuse as main transcript	c.*190T>C	3_prime_UTR_variant	3/3	1	NM_004373.4	ENSP00000229379.2	P12074
ENSG00000111780	ENST00000551806.1 linkuse as main transcript	c.174+2206T>C	intron_variant		3		ENSP00000450281.1	H0YIV9
COX6A1	ENST00000549525.1 linkuse as main transcript	n.757T>C	non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.730

AC:

110910

AN:

152030

Hom.:

41624

Cov.:

show subpopulations

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.:

AF XY:

0.676

AC XY:

124056

AN XY:

183494

show subpopulations

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.:

AF XY:

0.729

AC XY:

54243

AN XY:

74366

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over