chr1-70953013-T-G

Variant names:

• chr1-70953013-T-G
• rs762342468
• ENST00000356595.8:c.1151A>C

Variant summary

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

The ENST00000356595.8(PTGER3):​c.1151A>C​(p.His384Pro) 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. 14/19 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. H384L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTGER3 ENST00000356595.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860
• 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=0.107985556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTGER3	NM_198718.2	c.1151A>C	p.His384Pro	missense_variant	Exon 4 of 4		NP_942011.1
PTGER3	NM_001126044.2	c.*70A>C		3_prime_UTR_variant	Exon 5 of 5		NP_001119516.1
PTGER3	NM_198714.2	c.*23+750A>C		intron_variant	Intron 4 of 4		NP_942007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGER3	ENST00000356595.8	c.1151A>C	p.His384Pro	missense_variant	Exon 4 of 4	1		ENSP00000349003.4
PTGER3	ENST00000370931.7	c.*23+750A>C		intron_variant	Intron 4 of 4	1		ENSP00000359969.3
PTGER3	ENST00000460330.5	c.1104+750A>C		intron_variant	Intron 3 of 3	1		ENSP00000418073.1

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.53
DANN	Benign	0.22
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.91	T
PhyloP100		-0.86
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.021
Sift	Benign	0.13	T
Sift4G	Benign	0.22	T
Vest4		0.069
MutPred		0.47		Loss of MoRF binding (P = 0.0693);
MVP		0.093
MPC		1.1
ClinPred		0.030	T
GERP RS		-0.32
gMVP		0.27
Mutation Taster		=100/0	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: rs762342468; hg19: chr1-71418696;