NM_000959.4:c.653T>C

Variant names:

• chr1-78493396-T-C
• rs115994459
• NM_000959.4:c.653T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000959.4(PTGFR):​c.653T>C​(p.Leu218Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000771 in 1,613,852 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00042 (2 hom.)
• Consequence: PTGFR NM_000959.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.94
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074677765).
• BP6: Variant 1-78493396-T-C is Benign according to our data. Variant chr1-78493396-T-C is described in ClinVar as Benign. ClinVar VariationId is 711770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000959.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGFR	NM_000959.4	MANE Select	c.653T>C	p.Leu218Ser	missense	Exon 2 of 3	NP_000950.1	P43088-1
	PTGFR	NM_001039585.2		c.653T>C	p.Leu218Ser	missense	Exon 2 of 4	NP_001034674.1	P43088-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGFR	ENST00000370757.8	TSL:1 MANE Select	c.653T>C	p.Leu218Ser	missense	Exon 2 of 3	ENSP00000359793.3	P43088-1
	PTGFR	ENST00000370758.5	TSL:1	c.653T>C	p.Leu218Ser	missense	Exon 3 of 4	ENSP00000359794.1	P43088-1
	PTGFR	ENST00000370756.3	TSL:1	c.653T>C	p.Leu218Ser	missense	Exon 2 of 4	ENSP00000359792.3	P43088-2

Frequencies

GnomAD3 genomes AF: 0.00416 AC: 634 AN: 152236 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00109 AC: 273 AN: 250118 AF XY: 0.000717

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.000667

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000418 AC: 611 AN: 1461498 Hom.: 2 Cov.: 31 AF XY: 0.000347 AC XY: 252 AN XY: 727016

African (AFR) AF: 0.0146 AC: 488 AN: 33446

American (AMR) AF: 0.000873 AC: 39 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111874

Other (OTH) AF: 0.00104 AC: 63 AN: 60380

GnomAD4 genome AF: 0.00415 AC: 633 AN: 152354 Hom.: 7 Cov.: 33 AF XY: 0.00393 AC XY: 293 AN XY: 74514

African (AFR) AF: 0.0141 AC: 588 AN: 41582

American (AMR) AF: 0.00242 AC: 37 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00155 Hom.: 7

Bravo AF: 0.00520

ESP6500AA AF: 0.0132 AC: 58

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00129 AC: 157

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.9
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.044
Sift	Benign	0.056	T
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.23
MVP		0.043
MPC		0.31
ClinPred		0.017	T
GERP RS		4.7
Varity_R		0.075
gMVP		0.69
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs115994459; hg19: chr1-78959081;