Genetic Variant PAEP:p.Pro68Pro (chr9-135562401-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002571.4(PAEP):c.204C>T(p.Pro68Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,614,048 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 5 hom. )

Consequence

PAEP
NM_002571.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.77

Variant links:

Genes affected

PAEP (HGNC:8573): (progestagen associated endometrial protein) This gene is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The encoded glycoprotein has been previously referred to as pregnancy-associated endometrial alpha-2-globulin, placental protein 14, and glycodelin, but has been officially named progestagen-associated endometrial protein. Three distinct forms, with identical protein backbones but different glycosylation profiles, are found in amniotic fluid, follicular fluid and seminal plasma of the reproductive system. These glycoproteins have distinct and essential roles in regulating a uterine environment suitable for pregnancy and in the timing and occurrence of the appropriate sequence of events in the fertilization process. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

PAEP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 9-135562401-C-T is Benign according to our data. Variant chr9-135562401-C-T is described in ClinVar as [Benign]. Clinvar id is 717079.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.77 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAEP	NM_002571.4 link	c.204C>T	p.Pro68Pro	synonymous_variant	Exon 2 of 7	ENST00000479141.6	NP_002562.2	P09466-1A0A024R8D8B2R4F9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAEP	ENST00000479141.6 link	c.204C>T	p.Pro68Pro	synonymous_variant	Exon 2 of 7	1	NM_002571.4	ENSP00000417898.1		P09466-1
PAEP	ENST00000371766.6 link	c.204C>T	p.Pro68Pro	synonymous_variant	Exon 2 of 7	1		ENSP00000360831.1		P09466-1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00170

AC:

427

AN:

251250

Hom.:

AF XY:

0.00178

AC XY:

241

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00550

Gnomad NFE exome

AF:

0.00253

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.00204

AC:

2982

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

1423

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00521

Gnomad4 NFE exome

AF:

0.00233

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152286

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.000910

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 06, 2018

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

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.7

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over