19-36151719-C-A

Variant names:

Variant summary

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

The NM_001864.4(COX7A1):c.52G>T(p.Ala18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,391,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 30)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

COX7A1
NM_001864.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.09

Variant links:

Genes affected

COX7A1 (HGNC:2287): (cytochrome c oxidase subunit 7A1) 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 polypeptide 1 (muscle isoform) of subunit VIIa and the polypeptide 1 is present only in muscle tissues. Other polypeptides of subunit VIIa are present in both muscle and nonmuscle tissues, and are encoded by different genes. [provided by RefSeq, Jul 2008]

COX7A1 links:

Genome browser will be placed here

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=0.026728839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX7A1	NM_001864.4 link	c.52G>T	p.Ala18Ser	missense_variant	Exon 2 of 4	ENST00000292907.8	NP_001855.1	P24310Q6FGI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COX7A1	ENST00000292907.8 link	c.52G>T	p.Ala18Ser	missense_variant	Exon 2 of 4	1	NM_001864.4	ENSP00000292907.3	P24310
COX7A1	ENST00000589154.1 link	c.52G>T	p.Ala18Ser	missense_variant	Exon 2 of 4	5		ENSP00000468063.3	K7ER11
COX7A1	ENST00000437291.6 link	c.-117G>T		5_prime_UTR_variant	Exon 2 of 4	3		ENSP00000475885.1	U3KQH8
COX7A1	ENST00000481297.1 link	n.94G>T		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0000152

AC:

AN:

131788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000428

AC:

AN:

233690

Hom.:

AF XY:

0.00000787

AC XY:

AN XY:

127112

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:

0.0000341

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.94e-7

AC:

AN:

1260160

Hom.:

Cov.:

AF XY:

0.00000160

AC XY:

AN XY:

624412

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000152

AC:

AN:

131788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62512

show subpopulations

Gnomad4 AFR

AF:

0.0000557

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.52G>T (p.A18S) alteration is located in exon 2 (coding exon 2) of the COX7A1 gene. This alteration results from a G to T substitution at nucleotide position 52, causing the alanine (A) at amino acid position 18 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.5

DANN

Benign

0.85

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

0.42

N;.

REVEL

Benign

0.034

Sift

Benign

1.0

T;.

Sift4G

Benign

0.79

T;.

Polyphen

0.13

B;.

Vest4

0.14

MutPred

0.24

Gain of phosphorylation at A18 (P = 0.0254);Gain of phosphorylation at A18 (P = 0.0254);

MVP

0.030

MPC

0.45

ClinPred

0.033

GERP RS

1.1

Varity_R

0.020

gMVP

0.29

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