9-122381513-C-A

Variant names:

• chr9-122381513-C-A
• rs5788
• NM_000962.4:c.639C>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000962.4(PTGS1):​c.639C>A​(p.Gly213Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,884 control chromosomes in the GnomAD database, including 27,432 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. Synonymous variant affecting the same amino acid position (i.e. G213G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.27 (8808 hom., cov: 32)
  • Exomes 𝑓: 0.14 (18624 hom.)
• Consequence: PTGS1 NM_000962.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 56 publications found

Genes affected

PTGS1 (HGNC:9604): (prostaglandin-endoperoxide synthase 1) This is one of two genes encoding similar enzymes that catalyze the conversion of arachidonate to prostaglandin. The encoded protein regulates angiogenesis in endothelial cells, and is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin. Based on its ability to function as both a cyclooxygenase and as a peroxidase, the encoded protein has been identified as a moonlighting protein. The protein may promote cell proliferation during tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2021]

PTGS1 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 12

  Inheritance: SD, AD, AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=-0.377 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	NM_000962.4	MANE Select	c.639C>A	p.Gly213Gly	synonymous	Exon 6 of 11	NP_000953.2
	PTGS1	NM_080591.3		c.639C>A	p.Gly213Gly	synonymous	Exon 6 of 11	NP_542158.1	P23219-2
	PTGS1	NM_001271164.2		c.495C>A	p.Gly165Gly	synonymous	Exon 5 of 10	NP_001258093.1	A0A087X296

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGS1	ENST00000362012.7	TSL:1 MANE Select	c.639C>A	p.Gly213Gly	synonymous	Exon 6 of 11	ENSP00000354612.2	P23219-1
	PTGS1	ENST00000223423.8	TSL:1	c.639C>A	p.Gly213Gly	synonymous	Exon 6 of 11	ENSP00000223423.4	P23219-2
	PTGS1	ENST00000863393.1		c.693C>A	p.Gly231Gly	synonymous	Exon 7 of 12	ENSP00000533452.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40644 AN: 151960 Hom.: 8768 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0441

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.165 AC: 41416 AN: 251428 AF XY: 0.150

Gnomad AFR exome AF: 0.611

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.0474

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.137 AC: 200339 AN: 1461806 Hom.: 18624 Cov.: 33 AF XY: 0.135 AC XY: 97936 AN XY: 727206

African (AFR) AF: 0.616 AC: 20609 AN: 33472

American (AMR) AF: 0.224 AC: 10037 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3276 AN: 26136

East Asian (EAS) AF: 0.0368 AC: 1461 AN: 39700

South Asian (SAS) AF: 0.0918 AC: 7916 AN: 86252

European-Finnish (FIN) AF: 0.132 AC: 7045 AN: 53420

Middle Eastern (MID) AF: 0.148 AC: 854 AN: 5768

European-Non Finnish (NFE) AF: 0.126 AC: 140000 AN: 1111942

Other (OTH) AF: 0.151 AC: 9141 AN: 60392

GnomAD4 genome AF: 0.268 AC: 40741 AN: 152078 Hom.: 8808 Cov.: 32 AF XY: 0.263 AC XY: 19575 AN XY: 74334

African (AFR) AF: 0.596 AC: 24695 AN: 41438

American (AMR) AF: 0.241 AC: 3691 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3470

East Asian (EAS) AF: 0.0442 AC: 229 AN: 5180

South Asian (SAS) AF: 0.0868 AC: 418 AN: 4818

European-Finnish (FIN) AF: 0.131 AC: 1383 AN: 10584

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9253 AN: 67984

Other (OTH) AF: 0.243 AC: 513 AN: 2114

Alfa AF: 0.210 Hom.: 9992

Bravo AF: 0.290

Asia WGS AF: 0.117 AC: 408 AN: 3478

EpiCase AF: 0.121

EpiControl AF: 0.123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	7.3
DANN	Benign	0.74
PhyloP100		-0.38
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: rs5788; hg19: chr9-125143792; COSMIC: COSV56290751;