Variant 2-42361096-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004718.4(COX7A2L):c.66C>A(p.Ser22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

COX7A2L
NM_004718.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

COX7A2L (HGNC:2289): (cytochrome c oxidase subunit 7A2 like) Cytochrome c oxidase (COX), 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 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 function in the regulation and assembly of the complex. This nuclear gene encodes a protein similar to polypeptides 1 and 2 of subunit VIIa in the C-terminal region, and also highly similar to the mouse Sig81 protein sequence. This gene is expressed in all tissues, and upregulated in a breast cancer cell line after estrogen treatment. It is possible that this gene represents a regulatory subunit of COX and mediates the higher level of energy production in target cells by estrogen. Several transcript variants, some protein-coding and others non-protein coding, have been found for this gene. [provided by RefSeq, Jan 2016]

COX7A2L links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06058827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX7A2L	NM_004718.4 linkuse as main transcript	c.66C>A	p.Ser22Arg	missense_variant	1/3	ENST00000234301.3	NP_004709.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX7A2L	ENST00000234301.3 linkuse as main transcript	c.66C>A	p.Ser22Arg	missense_variant	1/3	1	NM_004718.4	ENSP00000234301	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250098

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135298

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461346

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726906

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2024

The c.66C>A (p.S22R) alteration is located in exon 1 (coding exon 1) of the COX7A2L gene. This alteration results from a C to A substitution at nucleotide position 66, causing the serine (S) at amino acid position 22 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.044

.;T;T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.85

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.82

T;.;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L;L;.

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.5

D;N;N;D

REVEL

Benign

0.055

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.085

T;T;T;T

Polyphen

0.024

.;B;B;.

Vest4

0.23, 0.41, 0.40

MutPred

0.23

.;Loss of ubiquitination at K27 (P = 0.0345);Loss of ubiquitination at K27 (P = 0.0345);Loss of ubiquitination at K27 (P = 0.0345);

MVP

0.23

MPC

0.0071

ClinPred

0.078

GERP RS

-0.10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.46

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