Genetic Variant NM_006601.7:c.187-82G>A (chr12-56671929-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006601.7(PTGES3):c.187-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 834,916 control chromosomes in the GnomAD database, including 194,710 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 0.70 ( 37276 hom., cov: 31)

Exomes 𝑓: 0.68 ( 157434 hom. )

Consequence

PTGES3
NM_006601.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27

Publications

32 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.771 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PTGES3	NM_006601.7	MANE Select	c.187-82G>A	intron	N/A	NP_006592.3
PTGES3	NM_001282604.2		c.199-82G>A	intron	N/A	NP_001269533.1
PTGES3	NM_001282601.2		c.187-82G>A	intron	N/A	NP_001269530.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PTGES3	ENST00000262033.11	TSL:1 MANE Select	c.187-82G>A	intron	N/A	ENSP00000262033.6
PTGES3	ENST00000456859.2	TSL:2	c.117-120G>A	intron	N/A	ENSP00000389090.2
PTGES3	ENST00000614328.4	TSL:3	c.199-82G>A	intron	N/A	ENSP00000482075.1

Frequencies

GnomAD3 genomes

AF:

0.699

AC:

106122

AN:

151864

Hom.:

37254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.737

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.731

Gnomad ASJ

AF:

0.633

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.793

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.697

GnomAD4 exome

AF:

0.677

AC:

462351

AN:

682934

Hom.:

157434

AF XY:

0.679

AC XY:

232254

AN XY:

342138

show subpopulations

African (AFR)

AF:

0.747

AC:

11213

AN:

15016

American (AMR)

AF:

0.752

AC:

10291

AN:

13680

Ashkenazi Jewish (ASJ)

AF:

0.654

AC:

8768

AN:

13416

East Asian (EAS)

AF:

0.699

AC:

19364

AN:

27704

South Asian (SAS)

AF:

0.796

AC:

20443

AN:

25682

European-Finnish (FIN)

AF:

0.708

AC:

29117

AN:

41142

Middle Eastern (MID)

AF:

0.664

AC:

2505

AN:

3770

European-Non Finnish (NFE)

AF:

0.664

AC:

339970

AN:

512030

Other (OTH)

AF:

0.678

AC:

20680

AN:

30494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

7253

14506

21758

29011

36264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8086

16172

24258

32344

40430

<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:

0.699

AC:

106197

AN:

151982

Hom.:

37276

Cov.:

AF XY:

0.703

AC XY:

52230

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.737

AC:

30548

AN:

41460

American (AMR)

AF:

0.731

AC:

11142

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.633

AC:

2195

AN:

3468

East Asian (EAS)

AF:

0.744

AC:

3847

AN:

5170

South Asian (SAS)

AF:

0.792

AC:

3818

AN:

4820

European-Finnish (FIN)

AF:

0.718

AC:

7569

AN:

10544

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.658

AC:

44727

AN:

67970

Other (OTH)

AF:

0.700

AC:

1476

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1629

3257

4886

6514

8143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<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:

0.677

Hom.:

68899

Bravo

AF:

0.699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.37

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over