Variant 1-78536619-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000959.4(PTGFR):c.1012A>G(p.Ile338Val) variant causes a missense change. The variant allele was found at a frequency of 0.00483 in 1,613,254 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 28 hom. )

Consequence

PTGFR
NM_000959.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.99

Variant links:

Genes affected

PTGFR (HGNC:9600): (prostaglandin F receptor) The protein encoded by this gene is member of the G-protein coupled receptor family. This protein is a receptor for prostaglandin F2-alpha (PGF2-alpha), which is known to be a potent luteolytic agent, and may also be involved in modulating intraocular pressure and smooth muscle contraction in uterus. Knockout studies in mice suggest that the interaction of PGF2-alpha with this receptor may initiate parturition in ovarian luteal cells and thus induce luteolysis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PTGFR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076702535).

BP6

Variant 1-78536619-A-G is Benign according to our data. Variant chr1-78536619-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638894.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PTGFR	NM_000959.4 linkuse as main transcript	c.1012A>G	p.Ile338Val	missense_variant	3/3	ENST00000370757.8	NP_000950.1
PTGFR	XM_047426085.1 linkuse as main transcript	c.1012A>G	p.Ile338Val	missense_variant	3/3		XP_047282041.1
PTGFR	NM_001039585.2 linkuse as main transcript	c.*189A>G		3_prime_UTR_variant	4/4		NP_001034674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGFR	ENST00000370757.8 linkuse as main transcript	c.1012A>G	p.Ile338Val	missense_variant	3/3	1	NM_000959.4	ENSP00000359793	P1	P43088-1
PTGFR	ENST00000370758.5 linkuse as main transcript	c.1012A>G	p.Ile338Val	missense_variant	4/4	1		ENSP00000359794	P1	P43088-1
PTGFR	ENST00000370756.3 linkuse as main transcript	c.*189A>G		3_prime_UTR_variant	4/4	1		ENSP00000359792		P43088-2
PTGFR	ENST00000497923.5 linkuse as main transcript	c.*330A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	3		ENSP00000432599

Frequencies

GnomAD3 genomes

AF:

0.00324

AC:

493

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00616

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00309

AC:

773

AN:

250098

Hom.:

AF XY:

0.00316

AC XY:

427

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000523

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000694

Gnomad NFE exome

AF:

0.00606

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00499

AC:

7291

AN:

1460976

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

3541

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.000718

Gnomad4 AMR exome

AF:

0.000493

Gnomad4 ASJ exome

AF:

0.00192

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.00621

Gnomad4 OTH exome

AF:

0.00360

GnomAD4 genome

AF:

0.00324

AC:

493

AN:

152278

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00616

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00505

Hom.:

Bravo

AF:

0.00317

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00376

AC:

456

EpiCase

AF:

0.00480

EpiControl

AF:

0.00540

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

PTGFR: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-0.021

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.0077

T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.9

M;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.28

Sift

Benign

0.053

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.020

B;B

Vest4

0.29

MVP

0.60

MPC

0.18

ClinPred

0.018

GERP RS

4.7

Varity_R

0.12

gMVP

0.37

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over