chr12-56684836-A-G

Position:

• chr12-56684836-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGES3	NM_006601.7	c.2+3162T>C		intron_variant		ENST00000262033.11	NP_006592.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGES3	ENST00000262033.11	c.2+3162T>C		intron_variant		1	NM_006601.7	ENSP00000262033	P1

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

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.614

Alfa AF: 0.531 Hom.: 2340

Bravo AF: 0.569

Asia WGS AF: 0.734 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs2290893; hg19: chr12-57078620;