Genetic Variant NM_198719.2:c.121C>G (chr1-71047457-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198719.2(PTGER3):c.121C>G(p.Pro41Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,696 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: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PTGER3
NM_198719.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.986

Variant links:

Genes affected

PTGER3 (HGNC:9595): (prostaglandin E receptor 3) 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). This receptor may have many biological functions, which involve digestion, nervous system, kidney reabsorption, and uterine contraction activities. Studies of the mouse counterpart suggest that this receptor may also mediate adrenocorticotropic hormone response as well as fever generation in response to exogenous and endogenous stimuli. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

PTGER3 links:

ZRANB2-AS1 (HGNC:43594): (ZRANB2 antisense RNA 1)

ZRANB2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.060032338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER3	NM_198719.2 link	c.121C>G	p.Pro41Ala	missense_variant	Exon 1 of 4	ENST00000306666.10	NP_942012.1	P43115-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGER3	ENST00000306666.10 link	c.121C>G	p.Pro41Ala	missense_variant	Exon 1 of 4	1	NM_198719.2	ENSP00000302313.5		P43115-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000423

AC:

AN:

236676

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000569

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:

6.86e-7

AC:

AN:

1457696

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724808

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.121C>G (p.P41A) alteration is located in exon 1 (coding exon 1) of the PTGER3 gene. This alteration results from a C to G substitution at nucleotide position 121, causing the proline (P) at amino acid position 41 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

0.053

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.1

DANN

Benign

0.85

DEOGEN2

Benign

0.11

T;.;.;.;.;T;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.74

.;T;T;T;T;.;T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.060

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

N;N;.;N;N;N;N;.;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.17

N;.;N;N;N;N;N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.12

T;.;T;T;T;T;T;T;T

Sift4G

Benign

0.23

T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;B;.;B;.;B;B;.;.

Vest4

0.099

MutPred

0.34

Loss of glycosylation at P41 (P = 0.0533);Loss of glycosylation at P41 (P = 0.0533);Loss of glycosylation at P41 (P = 0.0533);Loss of glycosylation at P41 (P = 0.0533);Loss of glycosylation at P41 (P = 0.0533);Loss of glycosylation at P41 (P = 0.0533);Loss of glycosylation at P41 (P = 0.0533);Loss of glycosylation at P41 (P = 0.0533);Loss of glycosylation at P41 (P = 0.0533);

MVP

0.35

MPC

0.69

ClinPred

0.031

GERP RS

-2.7

Varity_R

0.032

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over