chr1-70952977-C-G

Variant names:

• chr1-70952977-C-G
• rs369540225
• ENST00000356595.8:c.1187G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198718.2(PTGER3):​c.1187G>C​(p.Arg396Thr) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R396K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTGER3 NM_198718.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09891775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198718.2. 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
	PTGER3	NM_198718.2		c.1187G>C	p.Arg396Thr	missense	Exon 4 of 4	NP_942011.1	P43115-5
	PTGER3	NM_001126044.2		c.*106G>C		3_prime_UTR	Exon 5 of 5	NP_001119516.1	P43115-1
	PTGER3	NM_198714.2		c.*23+786G>C		intron	N/A	NP_942007.1	P43115-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGER3	ENST00000356595.8	TSL:1	c.1187G>C	p.Arg396Thr	missense	Exon 4 of 4	ENSP00000349003.4	P43115-5
	PTGER3	ENST00000370931.7	TSL:1	c.*23+786G>C		intron	N/A	ENSP00000359969.3	P43115-1
	PTGER3	ENST00000460330.5	TSL:1	c.1104+786G>C		intron	N/A	ENSP00000418073.1	P43115-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.57
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.017
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.016
Sift	Benign	0.074	T
Sift4G	Benign	0.34	T
Vest4		0.10
MutPred		0.48		Loss of MoRF binding (P = 0.0779)
MVP		0.068
MPC		1.0
ClinPred		0.055	T
GERP RS		-2.0
gMVP		0.16
Mutation Taster		=98/2	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: rs369540225; hg19: chr1-71418660;