5-40681033-C-T

Variant names:

• chr5-40681033-C-T
• rs768268072
• NM_000958.3:c.40C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000958.3(PTGER4):​c.40C>T​(p.Pro14Ser) 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. 17/22 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. P14A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTGER4 NM_000958.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 1 publications found

Genes affected

PTGER4 (HGNC:9596): (prostaglandin E receptor 4) 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 can activate T-cell factor signaling. It has been shown to mediate PGE2 induced expression of early growth response 1 (EGR1), regulate the level and stability of cyclooxygenase-2 mRNA, and lead to the phosphorylation of glycogen synthase kinase-3. Knockout studies in mice suggest that this receptor may be involved in the neonatal adaptation of circulatory system, osteoporosis, as well as initiation of skin immune responses. [provided by RefSeq, Jul 2008]

TTC33 (HGNC:29959): (tetratricopeptide repeat domain 33)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043693304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000958.3. 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
	PTGER4	NM_000958.3	MANE Select	c.40C>T	p.Pro14Ser	missense	Exon 2 of 3	NP_000949.1	P35408

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGER4	ENST00000302472.4	TSL:1 MANE Select	c.40C>T	p.Pro14Ser	missense	Exon 2 of 3	ENSP00000302846.3	P35408
	PTGER4	ENST00000514343.1	TSL:1	n.632C>T		non_coding_transcript_exon	Exon 2 of 2
	PTGER4	ENST00000963428.1		c.40C>T	p.Pro14Ser	missense	Exon 2 of 3	ENSP00000633487.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.28
DANN	Benign	0.90
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		-1.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.025
Sift	Benign	0.29	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.028
MutPred		0.30		Gain of loop (P = 0.0013)
MVP		0.41
MPC		1.2
ClinPred		0.070	T
GERP RS		-5.9
Varity_R		0.022
gMVP		0.44
Mutation Taster		=96/4	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: rs768268072; hg19: chr5-40681135;