1-71012411-T-C

Position:

• chr1-71012411-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198719.2(PTGER3):​c.971A>G​(p.Glu324Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PTGER3 NM_198719.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.70

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGER3	NM_198719.2	c.971A>G	p.Glu324Gly	missense_variant	2/4	ENST00000306666.10	NP_942012.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGER3	ENST00000306666.10	c.971A>G	p.Glu324Gly	missense_variant	2/4	1	NM_198719.2	ENSP00000302313.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461834 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

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

Feb 14, 2023

The c.971A>G (p.E324G) alteration is located in exon 2 (coding exon 2) of the PTGER3 gene. This alteration results from a A to G substitution at nucleotide position 971, causing the glutamic acid (E) at amino acid position 324 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	Uncertain	0.37
BayesDel_addAF	Benign	0.0061	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;.;.;.;.;T;T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	.;D;D;D;D;.;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M;M;.;M;M;M;M;.;M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D;.;D;D;D;D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.14	T;.;T;T;T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T;T;T;T;T
Polyphen		0.99	D;D;.;D;.;D;D;.;.
Vest4		0.54
MutPred		0.59		Loss of ubiquitination at K323 (P = 0.0472);Loss of ubiquitination at K323 (P = 0.0472);Loss of ubiquitination at K323 (P = 0.0472);Loss of ubiquitination at K323 (P = 0.0472);Loss of ubiquitination at K323 (P = 0.0472);Loss of ubiquitination at K323 (P = 0.0472);Loss of ubiquitination at K323 (P = 0.0472);Loss of ubiquitination at K323 (P = 0.0472);Loss of ubiquitination at K323 (P = 0.0472);
MVP		0.40
MPC		1.7
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.20
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1178993163; hg19: chr1-71478094;