Variant chr1-70953052-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198718.2(PTGER3):c.1112G>A(p.Cys371Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTGER3
NM_198718.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.65

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:

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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=0.093996495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
PTGER3	NM_198718.2 link	c.1112G>A	p.Cys371Tyr	missense_variant	4/4	NP_942011.1	P43115-5O00325
PTGER3	NM_001126044.2 link	c.*31G>A		3_prime_UTR_variant	5/5	NP_001119516.1	P43115-1
PTGER3	NM_198714.2 link	c.*23+711G>A		intron_variant		NP_942007.1	P43115-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
PTGER3	ENST00000356595.8 link	c.1112G>A	p.Cys371Tyr	missense_variant	4/4	1	ENSP00000349003.4	P43115-5
PTGER3	ENST00000370931.7 link	c.*23+711G>A		intron_variant		1	ENSP00000359969.3	P43115-1
PTGER3	ENST00000460330.5 link	c.1104+711G>A		intron_variant		1	ENSP00000418073.1	P43115-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1439508

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715184

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:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.1112G>A (p.C371Y) alteration is located in exon 4 (coding exon 4) of the PTGER3 gene. This alteration results from a G to A substitution at nucleotide position 1112, causing the cysteine (C) at amino acid position 371 to be replaced by a tyrosine (Y). 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

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.84

DANN

Benign

0.80

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00079

LIST_S2

Benign

0.28

M_CAP

Benign

0.0016

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.37

REVEL

Benign

0.045

Sift

Uncertain

0.026

Sift4G

Benign

0.46

Vest4

0.13

MutPred

0.55

Gain of solvent accessibility (P = 0.019);

MVP

0.068

MPC

1.2

ClinPred

0.044

GERP RS

-1.2

gMVP

0.17

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over