Genetic Variant PTGES3:c.2+1116_2+1117delAT (chr12-56686880-CAT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_006601.7(PTGES3):c.2+1116_2+1117delAT variant causes a intron 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_006601.7 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.435

Publications

4 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PTGES3	NM_006601.7 link	c.2+1116_2+1117delAT		intron_variant	Intron 1 of 7	ENST00000262033.11	NP_006592.3	Q15185-1A0A024RB32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTGES3	ENST00000262033.11 link	c.2+1116_2+1117delAT		intron_variant	Intron 1 of 7	1	NM_006601.7	ENSP00000262033.6		Q15185-1
PTGES3	ENST00000456859.2 link	c.2+1116_2+1117delAT		intron_variant	Intron 1 of 6	2		ENSP00000389090.2		B4DDC6

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86094

AN:

150976

Hom.:

26293

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.330

AC:

2369

AN:

7172

American (AMR)

AF:

0.667

AC:

4954

AN:

7428

Ashkenazi Jewish (ASJ)

AF:

0.598

AC:

5519

AN:

9232

East Asian (EAS)

AF:

0.686

AC:

15696

AN:

22880

South Asian (SAS)

AF:

0.772

AC:

2339

AN:

3030

European-Finnish (FIN)

AF:

0.699

AC:

14539

AN:

20796

Middle Eastern (MID)

AF:

0.607

AC:

783

AN:

1290

European-Non Finnish (NFE)

AF:

0.640

AC:

101066

AN:

157880

Other (OTH)

AF:

0.615

AC:

10062

AN:

16356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

2789

5577

8366

11154

13943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

386

772

1158

1544

1930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.570

AC:

86116

AN:

151094

Hom.:

26297

Cov.:

AF XY:

0.577

AC XY:

42572

AN XY:

73718

show subpopulations

African (AFR)

AF:

0.334

AC:

13780

AN:

41204

American (AMR)

AF:

0.671

AC:

10109

AN:

15060

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

2004

AN:

3470

East Asian (EAS)

AF:

0.742

AC:

3801

AN:

5122

South Asian (SAS)

AF:

0.746

AC:

3580

AN:

4800

European-Finnish (FIN)

AF:

0.711

AC:

7381

AN:

10374

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.640

AC:

43348

AN:

67774

Other (OTH)

AF:

0.604

AC:

1264

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1643

3286

4929

6572

8215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over