dbSNP rs3762883: COX18:p.Pro222Pro (chr4-73064835-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001297732.2(COX18):c.666C>T(p.Pro222Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,612,634 control chromosomes in the GnomAD database, including 146,648 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10562 hom., cov: 33)

Exomes 𝑓: 0.43 ( 136086 hom. )

Consequence

COX18
NM_001297732.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0820

Publications

17 publications found

Variant links:

Genes affected

COX18 (HGNC:26801): (cytochrome c oxidase assembly factor COX18) This gene encodes a cytochrome c oxidase assembly protein. The encoded protein is essential for integral membrane protein insertion into the mitochondrial inner membrane. It is also required for cytochrome c oxidase assembly and activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

COX18 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=-0.082 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX18	NM_001297732.2 link	c.666C>T	p.Pro222Pro	synonymous_variant	Exon 4 of 6	ENST00000507544.3	NP_001284661.1	B7ZL88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX18	ENST00000507544.3 link	c.666C>T	p.Pro222Pro	synonymous_variant	Exon 4 of 6	1	NM_001297732.2	ENSP00000425261.3		B7ZL88

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

55068

AN:

151930

Hom.:

10561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.440

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.397

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.441

Gnomad OTH

AF:

0.347

GnomAD2 exomes

AF:

0.391

AC:

98215

AN:

251342

AF XY:

0.402

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.402

Gnomad NFE exome

AF:

0.437

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.427

AC:

624207

AN:

1460586

Hom.:

136086

Cov.:

AF XY:

0.429

AC XY:

311691

AN XY:

726650

show subpopulations

African (AFR)

AF:

0.221

AC:

7377

AN:

33454

American (AMR)

AF:

0.270

AC:

12075

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

9335

AN:

26118

East Asian (EAS)

AF:

0.353

AC:

14010

AN:

39676

South Asian (SAS)

AF:

0.456

AC:

39340

AN:

86188

European-Finnish (FIN)

AF:

0.409

AC:

21790

AN:

53332

Middle Eastern (MID)

AF:

0.390

AC:

2247

AN:

5758

European-Non Finnish (NFE)

AF:

0.444

AC:

493597

AN:

1111012

Other (OTH)

AF:

0.405

AC:

24436

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

17110

34220

51331

68441

85551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.362

AC:

55075

AN:

152048

Hom.:

10562

Cov.:

AF XY:

0.359

AC XY:

26675

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.232

AC:

9605

AN:

41468

American (AMR)

AF:

0.312

AC:

4775

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1212

AN:

3470

East Asian (EAS)

AF:

0.373

AC:

1927

AN:

5172

South Asian (SAS)

AF:

0.455

AC:

2190

AN:

4816

European-Finnish (FIN)

AF:

0.397

AC:

4195

AN:

10562

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.441

AC:

29942

AN:

67964

Other (OTH)

AF:

0.343

AC:

724

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1818

3636

5453

7271

9089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.399

Hom.:

18161

Bravo

AF:

0.347

EpiCase

AF:

0.437

EpiControl

AF:

0.439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.4

(source)

DANN

Benign

0.86

PhyloP100

-0.082

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs3762883

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over