Genetic Variant PTGS1:p.Gly230Arg (chr9-122381673-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000962.4(PTGS1):c.688G>C(p.Gly230Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PTGS1
NM_000962.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.38

Publications

3 publications found

Variant links:

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 Classification: LIMITED Submitted by: ClinGen

PTGS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PTGS1	NM_000962.4	MANE Select	c.688G>C	p.Gly230Arg	missense	Exon 7 of 11	NP_000953.2
PTGS1	NM_080591.3		c.688G>C	p.Gly230Arg	missense	Exon 7 of 11	NP_542158.1
PTGS1	NM_001271164.2		c.544G>C	p.Gly182Arg	missense	Exon 6 of 10	NP_001258093.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PTGS1	ENST00000362012.7	TSL:1 MANE Select	c.688G>C	p.Gly230Arg	missense	Exon 7 of 11	ENSP00000354612.2
PTGS1	ENST00000223423.8	TSL:1	c.688G>C	p.Gly230Arg	missense	Exon 7 of 11	ENSP00000223423.4
PTGS1	ENST00000619306.5	TSL:5	c.544G>C	p.Gly182Arg	missense	Exon 6 of 10	ENSP00000483540.2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111994

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.58

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.97

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.59

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.6

PhyloP100

3.4

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.45

Sift

Benign

0.051

Sift4G

Uncertain

0.038

Polyphen

0.99

Vest4

0.85

MutPred

0.61

Gain of sheet (P = 0.1208)

MVP

0.91

MPC

1.0

ClinPred

0.96

GERP RS

4.8

Varity_R

0.81

gMVP

0.92

Mutation Taster

=71/29

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over