12-56686880-CAT-C

Position:

• chr12-56686880-CAT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001282604.2(PTGES3):​c.1_2delAT​(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 397,158 control chromosomes in the GnomAD database, including 77,071 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (26297 hom., cov: 0)
  • Exomes 𝑓: 0.64 (50774 hom.)
• Consequence: PTGES3 NM_001282604.2 frameshift, start_lost
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.435

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]

PTGES3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-56686880-CAT-C is Benign according to our data. Variant chr12-56686880-CAT-C is described in ClinVar as [Benign]. Clinvar id is 768555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGES3	NM_006601.7	c.2+1116_2+1117delAT		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+1116_2+1117delAT		intron_variant		1	NM_006601.7	ENSP00000262033.6
PTGES3	ENST00000456859.2	c.2+1116_2+1117delAT		intron_variant		2		ENSP00000389090.2

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86094 AN: 150976 Hom.: 26293 Cov.: 0

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.639 AC: 157327 AN: 246064 Hom.: 50774 AF XY: 0.641 AC XY: 79939 AN XY: 124668

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.598

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.772

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.640

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.570 AC: 86116 AN: 151094 Hom.: 26297 Cov.: 0 AF XY: 0.577 AC XY: 42572 AN XY: 73718

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.604

Alfa AF: 0.608 Hom.: 3605

Bravo AF: 0.556

Asia WGS AF: 0.732 AC: 2541 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs10579382; hg19: chr12-57080664;