Variant 11-82839298-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000313010.8(PRCP):c.1049C>A(p.Ala350Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000552 in 1,613,898 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 5 hom. )

Consequence

PRCP
ENST00000313010.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.24

Variant links:

Genes affected

PRCP (HGNC:9344): (prolylcarboxypeptidase) This gene encodes a member of the peptidase S28 family of serine exopeptidases. The encoded preproprotein is proteolytically processed to generate the mature lysosomal prolylcarboxypeptidase. This enzyme cleaves C-terminal amino acids linked to proline in peptides such as angiotension II, III and des-Arg9-bradykinin. The cleavage occurs at acidic pH, but the enzyme activity is retained with some substrates at neutral pH. This enzyme has been shown to be an activator of the cell matrix-associated prekallikrein. The importance of angiotension II, one of the substrates of this enzyme, in regulating blood pressure and electrolyte balance suggests that this gene may be related to essential hypertension. A pseudogene of this gene has been identified on chromosome 2. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

PRCP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0088401735).

BP6

Variant 11-82839298-G-T is Benign according to our data. Variant chr11-82839298-G-T is described in ClinVar as [Benign]. Clinvar id is 726101.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PRCP	NM_005040.4 linkuse as main transcript	c.1049C>A	p.Ala350Glu	missense_variant	7/9	ENST00000313010.8	NP_005031.1
PRCP	NM_199418.4 linkuse as main transcript	c.1112C>A	p.Ala371Glu	missense_variant	8/10		NP_955450.2
PRCP	NM_001319214.2 linkuse as main transcript	c.734C>A	p.Ala245Glu	missense_variant	6/8		NP_001306143.1
PRCP	XM_005274093.2 linkuse as main transcript	c.734C>A	p.Ala245Glu	missense_variant	7/9		XP_005274150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRCP	ENST00000313010.8 linkuse as main transcript	c.1049C>A	p.Ala350Glu	missense_variant	7/9	1	NM_005040.4	ENSP00000317362	P1	P42785-1

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

470

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000880

AC:

221

AN:

251084

Hom.:

AF XY:

0.000612

AC XY:

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000288

AC:

421

AN:

1461662

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

188

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.00309

AC:

470

AN:

152236

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

219

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000483

Hom.:

Bravo

AF:

0.00375

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000997

AC:

121

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

MetaRNN

Benign

0.0088

T;T

MetaSVM

Uncertain

0.099

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.41

Sift

Benign

0.21

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.22

B;.

Vest4

0.48

MVP

0.98

MPC

0.038

ClinPred

0.082

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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