1-78492772-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000959.4(PTGFR):c.29T>C(p.Val10Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000319 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: PTGFR NM_000959.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0580

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.009954333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGFR	NM_000959.4	c.29T>C	p.Val10Ala	missense_variant	2/3	ENST00000370757.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGFR	ENST00000370757.8	c.29T>C	p.Val10Ala	missense_variant	2/3	1	NM_000959.4	P1
PTGFR	ENST00000370758.5	c.29T>C	p.Val10Ala	missense_variant	3/4	1		P1
PTGFR	ENST00000370756.3	c.29T>C	p.Val10Ala	missense_variant	2/4	1
PTGFR	ENST00000497923.5	c.29T>C	p.Val10Ala	missense_variant, NMD_transcript_variant	2/5	3

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000295 AC: 74 AN: 251072 Hom.: 0 AF XY: 0.000302 AC XY: 41 AN XY: 135664

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000458

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000325 AC: 475 AN: 1461532 Hom.: 0 Cov.: 30 AF XY: 0.000337 AC XY: 245 AN XY: 727060

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.000689

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000365

Gnomad4 OTH exome AF: 0.000381

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152348 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74510

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000504 Hom.: 1

Bravo AF: 0.000295

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000189 AC: 23

EpiCase AF: 0.000763

EpiControl AF: 0.000593

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

Jul 09, 2021

The c.29T>C (p.V10A) alteration is located in exon 2 (coding exon 1) of the PTGFR gene. This alteration results from a T to C substitution at nucleotide position 29, causing the valine (V) at amino acid position 10 to be replaced by an alanine (A). 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	0.077
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.2
Dann	Benign	0.32
DEOGEN2	Benign	0.071	T;T;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.068	N
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.010	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.19	N;N;N
REVEL	Benign	0.032
Sift	Benign	0.98	T;T;T
Sift4G	Benign	0.80	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.037
MVP		0.093
MPC		0.26
ClinPred		0.019	T
GERP RS		1.9
Varity_R		0.043
gMVP		0.42

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: rs115647706; hg19: chr1-78958457;