Variant rs3842789 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000962.4(PTGS1):c.158G>A(p.Arg53His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

PTGS1
NM_000962.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.108

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 links:

PTGS1 (HGNC:):

PTGS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010848433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGS1	NM_000962.4 linkuse as main transcript	c.158G>A	p.Arg53His	missense_variant	3/11	ENST00000362012.7	NP_000953.2	P23219-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGS1	ENST00000362012.7 linkuse as main transcript	c.158G>A	p.Arg53His	missense_variant	3/11	1	NM_000962.4	ENSP00000354612.2		P23219-1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000263

AC:

AN:

251174

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000103

AC:

151

AN:

1461638

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.00106

AC:

162

AN:

152322

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00358

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000167

Hom.:

Bravo

AF:

0.00100

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.26

.;T;T;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.65

T;.;T;D;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.050

.;N;N;.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.44

N;.;N;.;N

REVEL

Benign

0.12

Sift

Benign

0.40

T;.;T;.;T

Sift4G

Benign

0.23

T;T;T;.;T

Polyphen

0.0, 0.0010

.;B;B;.;B

Vest4

0.17

MVP

0.69

MPC

0.34

ClinPred

0.0094

GERP RS

-0.22

Varity_R

0.099

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over