chr12-56684836-A-G

Variant names:

• chr12-56684836-A-G
• rs2290893
• NM_006601.7:c.2+3162T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006601.7(PTGES3):​c.2+3162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,016 control chromosomes in the GnomAD database, including 27,167 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (27167 hom., cov: 32)
• Consequence: PTGES3 NM_006601.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• Publications: 13 publications found

Genes affected

PTGES3 (HGNC:16049): (prostaglandin E synthase 3) This gene encodes an enzyme that converts prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). This protein functions as a co-chaperone with heat shock protein 90 (HSP90), localizing to response elements in DNA and disrupting transcriptional activation complexes. Alternative splicing results in multiple transcript variants. There are multiple pseudogenes of this gene on several different chromosomes. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006601.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES3	NM_006601.7	MANE Select	c.2+3162T>C		intron	N/A	NP_006592.3
	PTGES3	NM_001282604.2		c.14+2033T>C		intron	N/A	NP_001269533.1
	PTGES3	NM_001282601.2		c.2+3162T>C		intron	N/A	NP_001269530.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGES3	ENST00000262033.11	TSL:1 MANE Select	c.2+3162T>C		intron	N/A	ENSP00000262033.6
	PTGES3	ENST00000456859.2	TSL:2	c.2+3162T>C		intron	N/A	ENSP00000389090.2
	PTGES3	ENST00000614328.4	TSL:3	c.14+2033T>C		intron	N/A	ENSP00000482075.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88459 AN: 151898 Hom.: 27163 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.611

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.582 AC: 88484 AN: 152016 Hom.: 27167 Cov.: 32 AF XY: 0.589 AC XY: 43755 AN XY: 74300

African (AFR) AF: 0.374 AC: 15482 AN: 41440

American (AMR) AF: 0.677 AC: 10336 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2020 AN: 3472

East Asian (EAS) AF: 0.742 AC: 3843 AN: 5176

South Asian (SAS) AF: 0.745 AC: 3595 AN: 4828

European-Finnish (FIN) AF: 0.712 AC: 7522 AN: 10566

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43531 AN: 67964

Other (OTH) AF: 0.614 AC: 1296 AN: 2110

Alfa AF: 0.523 Hom.: 2395

Bravo AF: 0.569

Asia WGS AF: 0.734 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.39
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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: rs2290893; hg19: chr12-57078620;