Variant 1-78493420-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000370757.8(PTGFR):c.677C>G(p.Thr226Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,016 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PTGFR
ENST00000370757.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGFR	NM_000959.4 linkuse as main transcript	c.677C>G	p.Thr226Arg	missense_variant	2/3	ENST00000370757.8	NP_000950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGFR	ENST00000370757.8 linkuse as main transcript	c.677C>G	p.Thr226Arg	missense_variant	2/3	1	NM_000959.4	ENSP00000359793	P1	P43088-1
PTGFR	ENST00000370758.5 linkuse as main transcript	c.677C>G	p.Thr226Arg	missense_variant	3/4	1		ENSP00000359794	P1	P43088-1
PTGFR	ENST00000370756.3 linkuse as main transcript	c.677C>G	p.Thr226Arg	missense_variant	2/4	1		ENSP00000359792		P43088-2
PTGFR	ENST00000497923.5 linkuse as main transcript	c.677C>G	p.Thr226Arg	missense_variant, NMD_transcript_variant	2/5	3		ENSP00000432599

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461016

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726678

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2023

The c.677C>G (p.T226R) alteration is located in exon 2 (coding exon 1) of the PTGFR gene. This alteration results from a C to G substitution at nucleotide position 677, causing the threonine (T) at amino acid position 226 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

0.0087

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

T;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

.;T;T

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.23

Sift

Benign

0.038

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.90

P;P;P

Vest4

0.48

MutPred

0.77

Gain of MoRF binding (P = 0.0089);Gain of MoRF binding (P = 0.0089);Gain of MoRF binding (P = 0.0089);

MVP

0.18

MPC

0.58

ClinPred

0.98

GERP RS

3.0

Varity_R

0.32

gMVP

0.71

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over