9-129748681-G-A

Variant names:

• chr9-129748681-G-A
• rs3205181
• NM_004878.5:c.183C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004878.5(PTGES):​c.183C>T​(p.Ser61Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 1,579,712 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (154 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (109 hom.)
• Consequence: PTGES NM_004878.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.44
• Publications: 3 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-129748681-G-A is Benign according to our data. Variant chr9-129748681-G-A is described in ClinVar as Benign. ClinVar VariationId is 768328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

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.183C>T	p.Ser61Ser	synonymous	Exon 2 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.183C>T	p.Ser61Ser	synonymous	Exon 2 of 3	ENSP00000342385.4	O14684
	PTGES	ENST00000481476.1	TSL:1	n.312C>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3627 AN: 152128 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00643 AC: 1375 AN: 213678 AF XY: 0.00457

Gnomad AFR exome AF: 0.0826

Gnomad AMR exome AF: 0.00566

Gnomad ASJ exome AF: 0.00146

Gnomad EAS exome AF: 0.00206

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000584

Gnomad OTH exome AF: 0.00378

GnomAD4 exome AF: 0.00255 AC: 3640 AN: 1427466 Hom.: 109 Cov.: 30 AF XY: 0.00226 AC XY: 1602 AN XY: 710206

African (AFR) AF: 0.0812 AC: 2485 AN: 30618

American (AMR) AF: 0.00679 AC: 250 AN: 36832

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 29 AN: 25062

East Asian (EAS) AF: 0.00228 AC: 83 AN: 36398

South Asian (SAS) AF: 0.0000861 AC: 7 AN: 81326

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53094

Middle Eastern (MID) AF: 0.00775 AC: 44 AN: 5676

European-Non Finnish (NFE) AF: 0.000360 AC: 396 AN: 1099498

Other (OTH) AF: 0.00585 AC: 345 AN: 58962

GnomAD4 genome AF: 0.0239 AC: 3641 AN: 152246 Hom.: 154 Cov.: 32 AF XY: 0.0231 AC XY: 1720 AN XY: 74448

African (AFR) AF: 0.0816 AC: 3388 AN: 41526

American (AMR) AF: 0.0108 AC: 165 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68018

Other (OTH) AF: 0.0161 AC: 34 AN: 2110

Alfa AF: 0.0128 Hom.: 61

Bravo AF: 0.0275

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.22
DANN	Benign	0.60
PhyloP100		-3.4
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3205181; hg19: chr9-132510960;