chr5-40692307-G-C

Position:

• chr5-40692307-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000958.3(PTGER4):​c.1396G>C​(p.Ala466Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTGER4 NM_000958.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.315

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

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=0.09745884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGER4	NM_000958.3	c.1396G>C	p.Ala466Pro	missense_variant	3/3	ENST00000302472.4	NP_000949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGER4	ENST00000302472.4	c.1396G>C	p.Ala466Pro	missense_variant	3/3	1	NM_000958.3	ENSP00000302846.3
TTC33	ENST00000637375.1	c.221+54491C>G		intron_variant		5		ENSP00000490134.1
TTC33	ENST00000636863.1	c.221+54491C>G		intron_variant		5		ENSP00000490389.1
TTC33	ENST00000636106.1	c.221+54491C>G		intron_variant		5		ENSP00000490018.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 01, 2024

The c.1396G>C (p.A466P) alteration is located in exon 3 (coding exon 2) of the PTGER4 gene. This alteration results from a G to C substitution at nucleotide position 1396, causing the alanine (A) at amino acid position 466 to be replaced by a proline (P). 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	Benign	0.077
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.10
Sift	Benign	0.12	T
Sift4G	Benign	0.29	T
Polyphen		0.41	B
Vest4		0.14
MutPred		0.14		Gain of glycosylation at A466 (P = 0.0103);
MVP		0.54
MPC		0.15
ClinPred		0.16	T
GERP RS		4.0
Varity_R		0.063
gMVP		0.26

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.

Other links and lift over

hg19: chr5-40692409;