19-14473612-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000955.3(PTGER1):ā€‹c.709C>Gā€‹(p.Arg237Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,462,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000027 ( 0 hom. )

Consequence

PTGER1
NM_000955.3 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.910
Variant links:
Genes affected
PTGER1 (HGNC:9593): (prostaglandin E receptor 1) The protein encoded by this gene is a member of the G protein-coupled receptor family. This protein is one of four receptors identified for prostaglandin E2 (PGE2). Through a phosphatidylinositol-calcium second messenger system, G-Q proteins mediate this receptor's activity. Knockout studies in mice suggested a role of this receptor in mediating algesia and in regulation of blood pressure. Studies in mice also suggested that this gene may mediate adrenocorticotropic hormone response to bacterial endotoxin. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06873107).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTGER1NM_000955.3 linkuse as main transcriptc.709C>G p.Arg237Gly missense_variant 2/3 ENST00000292513.4 NP_000946.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTGER1ENST00000292513.4 linkuse as main transcriptc.709C>G p.Arg237Gly missense_variant 2/31 NM_000955.3 ENSP00000292513 P1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152088
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000771
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000473
AC:
3
AN:
63380
Hom.:
0
AF XY:
0.0000271
AC XY:
1
AN XY:
36856
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000833
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
35
AN:
1310298
Hom.:
0
Cov.:
32
AF XY:
0.0000279
AC XY:
18
AN XY:
645354
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000865
Gnomad4 SAS exome
AF:
0.0000576
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.52e-7
Gnomad4 OTH exome
AF:
0.0000735
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000774
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000567

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 submitterclinical testingAmbry GeneticsNov 17, 2023The c.709C>G (p.R237G) alteration is located in exon 2 (coding exon 1) of the PTGER1 gene. This alteration results from a C to G substitution at nucleotide position 709, causing the arginine (R) at amino acid position 237 to be replaced by a glycine (G). 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
0.072
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.072
T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.46
T
M_CAP
Pathogenic
0.59
D
MetaRNN
Benign
0.069
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
0.92
N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.045
Sift
Uncertain
0.021
D
Sift4G
Benign
0.19
T
Polyphen
0.080
B
Vest4
0.11
MutPred
0.50
Gain of relative solvent accessibility (P = 0.0479);
MVP
0.45
MPC
1.0
ClinPred
0.11
T
GERP RS
3.0
Varity_R
0.26
gMVP
0.57

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs567385882; hg19: chr19-14584424; API