1-78536619-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000959.4(PTGFR):c.1012A>G(p.Ile338Val) variant causes a missense change. The variant allele was found at a frequency of 0.00483 in 1,613,254 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (28 hom.)
• Consequence: PTGFR NM_000959.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.99

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0076702535).
• BP6: Variant 1-78536619-A-G is Benign according to our data. Variant chr1-78536619-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGFR	NM_000959.4	c.1012A>G	p.Ile338Val	missense_variant	3/3	ENST00000370757.8
PTGFR	XM_047426085.1	c.1012A>G	p.Ile338Val	missense_variant	3/3
PTGFR	NM_001039585.2	c.*189A>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGFR	ENST00000370757.8	c.1012A>G	p.Ile338Val	missense_variant	3/3	1	NM_000959.4	P1
PTGFR	ENST00000370758.5	c.1012A>G	p.Ile338Val	missense_variant	4/4	1		P1
PTGFR	ENST00000370756.3	c.*189A>G		3_prime_UTR_variant	4/4	1
PTGFR	ENST00000497923.5	c.*330A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 493 AN: 152160 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00616

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00309 AC: 773 AN: 250098 Hom.: 2 AF XY: 0.00316 AC XY: 427 AN XY: 135134

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.000523

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000694

Gnomad NFE exome AF: 0.00606

Gnomad OTH exome AF: 0.00279

GnomAD4 exome AF: 0.00499 AC: 7291 AN: 1460976 Hom.: 28 Cov.: 30 AF XY: 0.00487 AC XY: 3541 AN XY: 726776

Gnomad4 AFR exome AF: 0.000718

Gnomad4 AMR exome AF: 0.000493

Gnomad4 ASJ exome AF: 0.00192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00126

Gnomad4 NFE exome AF: 0.00621

Gnomad4 OTH exome AF: 0.00360

GnomAD4 genome AF: 0.00324 AC: 493 AN: 152278 Hom.: 3 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74446

Gnomad4 AFR AF: 0.000962

Gnomad4 AMR AF: 0.000851

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00103

Gnomad4 NFE AF: 0.00616

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00505 Hom.: 2

Bravo AF: 0.00317

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00523 AC: 45

ExAC AF: 0.00376 AC: 456

EpiCase AF: 0.00480

EpiControl AF: 0.00540

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

PTGFR: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.11
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-0.021
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.0077	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.9	M;M
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.41	N;N
REVEL	Benign	0.28
Sift	Benign	0.053	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.020	B;B
Vest4		0.29
MVP		0.60
MPC		0.18
ClinPred		0.018	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.37

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: rs140723645; hg19: chr1-79002304; COSMIC: COSV99056354;