rs3762883

Variant names:

• chr4-73064835-G-A
• rs3762883
• NM_001297732.2:c.666C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-73064835-G-A
• chr4-73064835-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 17 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297732.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX18	NM_001297732.2	MANE Select	c.666C>T	p.Pro222Pro	synonymous	Exon 4 of 6	NP_001284661.1
	COX18	NM_001300729.1		c.672C>T	p.Pro224Pro	synonymous	Exon 3 of 5	NP_001287658.1
	COX18	NM_173827.4		c.663C>T	p.Pro221Pro	synonymous	Exon 4 of 6	NP_776188.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX18	ENST00000507544.3	TSL:1 MANE Select	c.666C>T	p.Pro222Pro	synonymous	Exon 4 of 6	ENSP00000425261.3
	COX18	ENST00000295890.8	TSL:1	c.663C>T	p.Pro221Pro	synonymous	Exon 4 of 6	ENSP00000295890.4
	COX18	ENST00000449739.6	TSL:1	n.*172C>T		non_coding_transcript_exon	Exon 3 of 5	ENSP00000394583.2

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55068 AN: 151930 Hom.: 10561 Cov.: 33

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

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.: 34 AF XY: 0.429 AC XY: 311691 AN XY: 726650

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

GnomAD4 genome AF: 0.362 AC: 55075 AN: 152048 Hom.: 10562 Cov.: 33 AF XY: 0.359 AC XY: 26675 AN XY: 74320

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.4
DANN	Benign	0.86
PhyloP100		-0.082
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3762883; hg19: chr4-73930552; COSMIC: COSV55720371; COSMIC: COSV55720371;