Genetic Variant PTGIR:p.Val347Leu (chr19-46621402-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000960.4(PTGIR):c.1039G>T(p.Val347Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,602,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V347M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PTGIR
NM_000960.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.98

Variant links:

Genes affected

PTGIR (HGNC:9602): (prostaglandin I2 receptor) The protein encoded by this gene is a member of the G-protein coupled receptor family 1 and has been shown to be a receptor for prostacyclin. Prostacyclin, the major product of cyclooxygenase in macrovascular endothelium, elicits a potent vasodilation and inhibition of platelet aggregation through binding to this receptor. [provided by RefSeq, Jul 2008]

PTGIR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20239252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGIR	NM_000960.4 link	c.1039G>T	p.Val347Leu	missense_variant	Exon 3 of 3	ENST00000291294.7	NP_000951.1	P43119

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTGIR	ENST00000291294.7 link	c.1039G>T	p.Val347Leu	missense_variant	Exon 3 of 3	1	NM_000960.4	ENSP00000291294.1	P43119
PTGIR	ENST00000598865.5 link	c.403G>T	p.Val135Leu	missense_variant	Exon 3 of 3	3		ENSP00000470799.1	M0QZW0
PTGIR	ENST00000594275.1 link	c.310G>T	p.Val104Leu	missense_variant	Exon 3 of 3	3		ENSP00000469408.1	M0QXV5
PTGIR	ENST00000597185.1 link	c.226G>T	p.Val76Leu	missense_variant	Exon 2 of 2	3		ENSP00000470566.1	M0QZI2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

244926

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000906

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449782

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;.;.

Eigen

Benign

0.0036

Eigen_PC

Benign

-0.022

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.30

N;.;.;.

REVEL

Benign

0.059

Sift

Benign

0.14

T;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.94

P;.;.;.

Vest4

0.23

MutPred

0.21

Loss of methylation at K342 (P = 0.1208);.;.;.;

MVP

0.78

MPC

0.25

ClinPred

0.66

GERP RS

2.5

Varity_R

0.066

gMVP

0.26

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