1-78493140-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000959.4(PTGFR):c.397C>T(p.Arg133Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
PTGFR
NM_000959.4 missense
NM_000959.4 missense
Scores
11
6
1
Clinical Significance
Conservation
PhyloP100: 2.44
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.979
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTGFR | NM_000959.4 | c.397C>T | p.Arg133Trp | missense_variant | 2/3 | ENST00000370757.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTGFR | ENST00000370757.8 | c.397C>T | p.Arg133Trp | missense_variant | 2/3 | 1 | NM_000959.4 | P1 | |
PTGFR | ENST00000370758.5 | c.397C>T | p.Arg133Trp | missense_variant | 3/4 | 1 | P1 | ||
PTGFR | ENST00000370756.3 | c.397C>T | p.Arg133Trp | missense_variant | 2/4 | 1 | |||
PTGFR | ENST00000497923.5 | c.397C>T | p.Arg133Trp | missense_variant, NMD_transcript_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251462Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727248
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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 | Jul 12, 2022 | The c.397C>T (p.R133W) alteration is located in exon 2 (coding exon 1) of the PTGFR gene. This alteration results from a C to T substitution at nucleotide position 397, causing the arginine (R) at amino acid position 133 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Uncertain
D;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of catalytic residue at C134 (P = 0.0857);Gain of catalytic residue at C134 (P = 0.0857);Gain of catalytic residue at C134 (P = 0.0857);
MVP
MPC
0.83
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at