1-78493247-G-T

Position:

• chr1-78493247-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000959.4(PTGFR):​c.504G>T​(p.Leu168Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTGFR NM_000959.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32482052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGFR	NM_000959.4	c.504G>T	p.Leu168Phe	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	c.504G>T	p.Leu168Phe	missense_variant	2/3	1	NM_000959.4	ENSP00000359793	P1
PTGFR	ENST00000370758.5	c.504G>T	p.Leu168Phe	missense_variant	3/4	1		ENSP00000359794	P1
PTGFR	ENST00000370756.3	c.504G>T	p.Leu168Phe	missense_variant	2/4	1		ENSP00000359792
PTGFR	ENST00000497923.5	c.504G>T	p.Leu168Phe	missense_variant, NMD_transcript_variant	2/5	3		ENSP00000432599

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.504G>T (p.L168F) alteration is located in exon 2 (coding exon 1) of the PTGFR gene. This alteration results from a G to T substitution at nucleotide position 504, causing the leucine (L) at amino acid position 168 to be replaced by a phenylalanine (F). 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	0.11
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	.;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.047	D;D;D
Sift4G	Benign	0.068	T;T;D
Polyphen		0.78	P;P;P
Vest4		0.056
MutPred		0.69		Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);
MVP		0.33
MPC		0.25
ClinPred		0.86	D
GERP RS		3.0
Varity_R		0.17
gMVP		0.52

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

Other links and lift over

dbSNP: rs1649460320; hg19: chr1-78958932;