6-75240349-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001366293.2(COX7A2):c.145G>A(p.Val49Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COX7A2
NM_001366293.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.44

Publications

0 publications found

Variant links:

Genes affected

COX7A2 (HGNC:2288): (cytochrome c oxidase subunit 7A2) Cytochrome c oxidase, the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of three catalytic subunits encoded by mitochondrial genes, and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, while the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes polypeptide 2 (liver isoform) of subunit VIIa, with this polypeptide being present in both muscle and non-muscle tissues. In addition to polypeptide 2, subunit VIIa includes polypeptide 1 (muscle isoform), which is present only in muscle tissues, and a related protein, which is present in all tissues. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4 and 14. [provided by RefSeq, Oct 2009]

COX7A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035525203).

BP6

Variant 6-75240349-C-T is Benign according to our data. Variant chr6-75240349-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2331700.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366293.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COX7A2	NM_001366293.2	MANE Select	c.145G>A	p.Val49Ile	missense	Exon 3 of 4	NP_001353222.1	P14406
COX7A2	NM_001366292.3		c.145G>A	p.Val49Ile	missense	Exon 4 of 5	NP_001353221.2	P14406
COX7A2	NM_001865.6		c.145G>A	p.Val49Ile	missense	Exon 4 of 5	NP_001856.3	P14406

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COX7A2	ENST00000684430.2	MANE Select	c.145G>A	p.Val49Ile	missense	Exon 3 of 4	ENSP00000506727.1	P14406
COX7A2	ENST00000370089.6	TSL:1	c.241G>A	p.Val81Ile	missense	Exon 3 of 4	ENSP00000359106.2	H0UI06
COX7A2	ENST00000899324.1		c.283G>A	p.Val95Ile	missense	Exon 4 of 5	ENSP00000569383.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458064

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33274

American (AMR)

AF:

0.00

AC:

AN:

44098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.00

AC:

AN:

85646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110576

Other (OTH)

AF:

0.00

AC:

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.0020

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.011

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.065

M_CAP

Benign

0.0052

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.1

PhyloP100

-1.4

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.29

REVEL

Benign

0.013

Sift

Benign

1.0

Sift4G

Benign

0.69

Vest4

0.10

MutPred

0.21

Gain of methylation at K46 (P = 0.0869)

MVP

0.040

MPC

0.064

ClinPred

0.048

GERP RS

-4.0

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

gMVP

0.14

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over