1-78493461-G-A

Position:

• chr1-78493461-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000959.4(PTGFR):​c.718G>A​(p.Gly240Ser) variant causes a missense change. 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: 5.24

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15407878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGFR	NM_000959.4	c.718G>A	p.Gly240Ser	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.718G>A	p.Gly240Ser	missense_variant	2/3	1	NM_000959.4	ENSP00000359793	P1
PTGFR	ENST00000370758.5	c.718G>A	p.Gly240Ser	missense_variant	3/4	1		ENSP00000359794	P1
PTGFR	ENST00000370756.3	c.718G>A	p.Gly240Ser	missense_variant	2/4	1		ENSP00000359792
PTGFR	ENST00000497923.5	c.718G>A	p.Gly240Ser	missense_variant, NMD_transcript_variant	2/5	3		ENSP00000432599

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

May 02, 2024

The c.718G>A (p.G240S) alteration is located in exon 2 (coding exon 1) of the PTGFR gene. This alteration results from a G to A substitution at nucleotide position 718, causing the glycine (G) at amino acid position 240 to be replaced by a serine (S). 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	0.23
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.56	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.42	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.91	P;P;D
Vest4		0.12
MutPred		0.30		Gain of disorder (P = 0.0674);Gain of disorder (P = 0.0674);Gain of disorder (P = 0.0674);
MVP		0.17
MPC		0.60
ClinPred		0.70	D
GERP RS		5.7
Varity_R		0.14
gMVP		0.69

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.

Other links and lift over

hg19: chr1-78959146; COSMIC: COSV66116684;