Genetic Variant NM_000960.4:c.610G>T (chr19-46623616-C-A) – 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_000960.4(PTGIR):c.610G>T(p.Gly204Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000903 in 1,549,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G204S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

PTGIR
NM_000960.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46

Publications

3 publications found

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 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_000960.4. 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
	PTGIR	NM_000960.4	MANE Select	c.610G>T	p.Gly204Cys	missense	Exon 2 of 3	NP_000951.1	P43119

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTGIR	ENST00000291294.7	TSL:1 MANE Select	c.610G>T	p.Gly204Cys	missense	Exon 2 of 3	ENSP00000291294.1	P43119
PTGIR	ENST00000872951.1		c.610G>T	p.Gly204Cys	missense	Exon 2 of 3	ENSP00000543010.1
PTGIR	ENST00000872954.1		c.610G>T	p.Gly204Cys	missense	Exon 2 of 3	ENSP00000543013.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152258

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

GnomAD4 exome

AF:

0.00000930

AC:

AN:

1397376

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689638

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31740

American (AMR)

AF:

0.00

AC:

AN:

35816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25166

East Asian (EAS)

AF:

0.00

AC:

AN:

35940

South Asian (SAS)

AF:

0.00

AC:

AN:

79388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.0000102

AC:

AN:

1079730

Other (OTH)

AF:

0.0000345

AC:

AN:

58006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.065

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.4

PhyloP100

1.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.92

REVEL

Uncertain

0.36

Sift

Benign

0.18

Sift4G

Benign

0.18

Polyphen

0.14

Vest4

0.47

MutPred

0.64

Loss of MoRF binding (P = 0.0831)

MVP

0.88

MPC

0.24

ClinPred

0.65

GERP RS

3.7

Varity_R

0.31

gMVP

0.71

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over