1-78493020-G-A

Position:

• chr1-78493020-G-A

Variant summary

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

The NM_000959.4(PTGFR):​c.277G>A​(p.Ala93Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict 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: 2.78

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 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	c.277G>A	p.Ala93Thr	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.277G>A	p.Ala93Thr	missense_variant	2/3	1	NM_000959.4	ENSP00000359793	P1
PTGFR	ENST00000370758.5	c.277G>A	p.Ala93Thr	missense_variant	3/4	1		ENSP00000359794	P1
PTGFR	ENST00000370756.3	c.277G>A	p.Ala93Thr	missense_variant	2/4	1		ENSP00000359792
PTGFR	ENST00000497923.5	c.277G>A	p.Ala93Thr	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 14, 2024

The c.277G>A (p.A93T) 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 277, causing the alanine (A) at amino acid position 93 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Benign	-0.0025	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;T;.
Eigen	Benign	0.082
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.0	M;M;M
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.43	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.97	D;D;P
Vest4		0.51
MutPred		0.53		Loss of catalytic residue at A93 (P = 0.0383);Loss of catalytic residue at A93 (P = 0.0383);Loss of catalytic residue at A93 (P = 0.0383);
MVP		0.63
MPC		0.68
ClinPred		0.67	D
GERP RS		4.9
Varity_R		0.11
gMVP		0.34

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: chr1-78958705;