9-129752951-G-C

Variant names:

• chr9-129752951-G-C
• rs201949041
• NM_004878.5:c.62C>G

Variant summary

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

The NM_004878.5(PTGES):​c.62C>G​(p.Thr21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T21M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTGES NM_004878.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92
• Publications: 0 publications found

Genes affected

PTGES (HGNC:9599): (prostaglandin E synthase) The protein encoded by this gene is a glutathione-dependent prostaglandin E synthase. The expression of this gene has been shown to be induced by proinflammatory cytokine interleukin 1 beta (IL1B). Its expression can also be induced by tumor suppressor protein TP53, and may be involved in TP53 induced apoptosis. Knockout studies in mice suggest that this gene may contribute to the pathogenesis of collagen-induced arthritis and mediate acute pain during inflammatory responses. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004878.5. 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
	PTGES	NM_004878.5	MANE Select	c.62C>G	p.Thr21Arg	missense	Exon 1 of 3	NP_004869.1	O14684

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES	ENST00000340607.5	TSL:1 MANE Select	c.62C>G	p.Thr21Arg	missense	Exon 1 of 3	ENSP00000342385.4	O14684
	PTGES	ENST00000481476.1	TSL:1	n.69C>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.023	D
Polyphen		0.97	D
Vest4		0.39
MutPred		0.73		Gain of MoRF binding (P = 0.0382)
MVP		0.70
MPC		1.5
ClinPred		0.99	D
GERP RS		3.6
PromoterAI		0.046	Neutral
Varity_R		0.94
gMVP		0.85
Mutation Taster		=49/51	disease causing

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: rs201949041; hg19: chr9-132515230;