Variant rs443751 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_023077.3(COA7):c.656A>G(p.Lys219Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,614,068 control chromosomes in the GnomAD database, including 94,528 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6885 hom., cov: 33)

Exomes 𝑓: 0.34 ( 87643 hom. )

Consequence

COA7
NM_023077.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.99

Variant links:

Genes affected

COA7 (HGNC:25716): (cytochrome c oxidase assembly factor 7) Located in mitochondrial intermembrane space and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

COA7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017867088).

BP6

Variant 1-52687760-T-C is Benign according to our data. Variant chr1-52687760-T-C is described in ClinVar as [Benign]. Clinvar id is 1287335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA7	NM_023077.3 link	c.656A>G	p.Lys219Arg	missense_variant	3/3	ENST00000371538.5	NP_075565.2	Q96BR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA7	ENST00000371538.5 link	c.656A>G	p.Lys219Arg	missense_variant	3/3	1	NM_023077.3	ENSP00000360593.3		Q96BR5
COA7	ENST00000486918.1 link	n.710A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43441

AN:

152108

Hom.:

6886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.0181

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.287

AC:

72192

AN:

251300

Hom.:

11906

AF XY:

0.297

AC XY:

40294

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.339

Gnomad EAS exome

AF:

0.0192

Gnomad SAS exome

AF:

0.323

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.338

AC:

493802

AN:

1461840

Hom.:

87643

Cov.:

AF XY:

0.338

AC XY:

245716

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.185

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.0174

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.347

Gnomad4 NFE exome

AF:

0.363

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.285

AC:

43449

AN:

152228

Hom.:

6885

Cov.:

AF XY:

0.281

AC XY:

20890

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.0185

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.347

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.335

Hom.:

23251

Bravo

AF:

0.271

TwinsUK

AF:

0.378

AC:

1400

ALSPAC

AF:

0.354

AC:

1366

ESP6500AA

AF:

0.200

AC:

879

ESP6500EA

AF:

0.355

AC:

3053

ExAC

AF:

0.293

AC:

35559

Asia WGS

AF:

0.163

AC:

570

AN:

3478

EpiCase

AF:

0.361

EpiControl

AF:

0.353

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.073

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.80

REVEL

Benign

0.072

Sift

Benign

0.28

Sift4G

Benign

0.43

Polyphen

0.0060

Vest4

0.11

MPC

0.12

ClinPred

0.0051

GERP RS

5.5

Varity_R

0.040

gMVP

0.32

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