9-122383706-C-A

Variant names:

• chr9-122383706-C-A
• rs145581212
• NM_000962.4:c.960C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_000962.4(PTGS1):​c.960C>A​(p.Pro320Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P320P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PTGS1 NM_000962.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820
• Publications: 0 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: AR, AD, SD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=-0.82 with no splicing effect.

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.960C>A	p.Pro320Pro	synonymous	Exon 8 of 11	NP_000953.2
	PTGS1	NM_080591.3		c.960C>A	p.Pro320Pro	synonymous	Exon 8 of 11	NP_542158.1	P23219-2
	PTGS1	NM_001271164.2		c.816C>A	p.Pro272Pro	synonymous	Exon 7 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.960C>A	p.Pro320Pro	synonymous	Exon 8 of 11	ENSP00000354612.2	P23219-1
	PTGS1	ENST00000223423.8	TSL:1	c.960C>A	p.Pro320Pro	synonymous	Exon 8 of 11	ENSP00000223423.4	P23219-2
	PTGS1	ENST00000863393.1		c.1014C>A	p.Pro338Pro	synonymous	Exon 9 of 12	ENSP00000533452.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152166 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251086 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461602 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727142

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152284 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	5.1
DANN	Benign	0.83
PhyloP100		-0.82

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

Other links and lift over

dbSNP: rs145581212; hg19: chr9-125145985;