NM_000962.4:c.960C>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000962.4(PTGS1):​c.960C>G​(p.Pro320Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0048 in 1,613,882 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0048 (27 hom.)
• Consequence: PTGS1 NM_000962.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: 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=-0.53).
• BP6: Variant 9-122383706-C-G is Benign according to our data. Variant chr9-122383706-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2659482.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.82 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 27 SD gene

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

Frequencies

GnomAD3 genomes AF: 0.00434 AC: 660 AN: 152162 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00622

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00441 AC: 1108 AN: 251086 AF XY: 0.00460

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0176

Gnomad NFE exome AF: 0.00562

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00485 AC: 7085 AN: 1461602 Hom.: 27 Cov.: 32 AF XY: 0.00462 AC XY: 3357 AN XY: 727142

African (AFR) AF: 0.000538 AC: 18 AN: 33480

American (AMR) AF: 0.000962 AC: 43 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86256

European-Finnish (FIN) AF: 0.0164 AC: 872 AN: 53156

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00531 AC: 5901 AN: 1111996

Other (OTH) AF: 0.00338 AC: 204 AN: 60390

GnomAD4 genome AF: 0.00433 AC: 660 AN: 152280 Hom.: 1 Cov.: 31 AF XY: 0.00459 AC XY: 342 AN XY: 74450

African (AFR) AF: 0.000674 AC: 28 AN: 41568

American (AMR) AF: 0.000915 AC: 14 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.0165 AC: 175 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00622 AC: 423 AN: 68014

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00347 Hom.: 0

Bravo AF: 0.00277

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00463

EpiControl AF: 0.00462

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		-0.82
Mutation Taster		=98/2	polymorphism

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;