rs443751

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

36 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

COA7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a chain Cytochrome c oxidase assembly factor 7 (size 229) in uniprot entity COA7_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_023077.3

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 VariationId 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 rank	MANE	Protein	UniProt
COA7	NM_023077.3 link	c.656A>G	p.Lys219Arg	missense_variant	Exon 3 of 3	ENST00000371538.5	NP_075565.2	Q96BR5

Ensembl

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

GnomAD2 exomes

AF:

0.287

AC:

72192

AN:

251300

AF XY:

0.297

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 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

African (AFR)

AF:

0.185

AC:

6208

AN:

33480

American (AMR)

AF:

0.168

AC:

7492

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

8892

AN:

26136

East Asian (EAS)

AF:

0.0174

AC:

690

AN:

39700

South Asian (SAS)

AF:

0.319

AC:

27517

AN:

86254

European-Finnish (FIN)

AF:

0.347

AC:

18560

AN:

53418

Middle Eastern (MID)

AF:

0.303

AC:

1747

AN:

5768

European-Non Finnish (NFE)

AF:

0.363

AC:

403378

AN:

1111976

Other (OTH)

AF:

0.320

AC:

19318

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

19166

38332

57499

76665

95831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12508

25016

37524

50032

62540

<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

AF:

0.285

AC:

43449

AN:

152228

Hom.:

6885

Cov.:

AF XY:

0.281

AC XY:

20890

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.193

AC:

8027

AN:

41540

American (AMR)

AF:

0.236

AC:

3609

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

1108

AN:

3472

East Asian (EAS)

AF:

0.0185

AC:

AN:

5184

South Asian (SAS)

AF:

0.315

AC:

1520

AN:

4828

European-Finnish (FIN)

AF:

0.347

AC:

3680

AN:

10606

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24526

AN:

67986

Other (OTH)

AF:

0.289

AC:

610

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1602

3204

4805

6407

8009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.330

Hom.:

41731

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

2.0

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

Mutation Taster

=81/19

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over