19-43649096-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002659.4(PLAUR):c.802A>G(p.Met268Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,614,122 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0044 ( 22 hom. )

Consequence

PLAUR
NM_002659.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

PLAUR (HGNC:9053): (plasminogen activator, urokinase receptor) This gene encodes the receptor for urokinase plasminogen activator and, given its role in localizing and promoting plasmin formation, likely influences many normal and pathological processes related to cell-surface plasminogen activation and localized degradation of the extracellular matrix. It binds both the proprotein and mature forms of urokinase plasminogen activator and permits the activation of the receptor-bound pro-enzyme by plasmin. The protein lacks transmembrane or cytoplasmic domains and may be anchored to the plasma membrane by a glycosyl-phosphatidylinositol (GPI) moiety following cleavage of the nascent polypeptide near its carboxy-terminus. However, a soluble protein is also produced in some cell types. Alternative splicing results in multiple transcript variants encoding different isoforms. The proprotein experiences several post-translational cleavage reactions that have not yet been fully defined. [provided by RefSeq, Jul 2008]

PLAUR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022387892).

BP6

Variant 19-43649096-T-C is Benign according to our data. Variant chr19-43649096-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 782626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-43649096-T-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAUR	NM_002659.4 link	c.802A>G	p.Met268Val	missense_variant	Exon 7 of 7	ENST00000340093.8	NP_002650.1	Q03405-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8 link	c.802A>G	p.Met268Val	missense_variant	Exon 7 of 7	1	NM_002659.4	ENSP00000339328.3		Q03405-1

Frequencies

GnomAD3 genomes

AF:

0.00359

AC:

547

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00500

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00361

AC:

907

AN:

251160

Hom.:

AF XY:

0.00370

AC XY:

502

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00468

Gnomad ASJ exome

AF:

0.00804

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00189

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00484

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00439

AC:

6421

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

3158

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00514

Gnomad4 ASJ exome

AF:

0.00884

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00167

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.00492

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.00359

AC:

547

AN:

152332

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000745

Gnomad4 AMR

AF:

0.00836

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00500

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00492

Hom.:

Bravo

AF:

0.00424

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00317

AC:

385

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00676

EpiControl

AF:

0.00693

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PLAUR: BP4, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.041

T;T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.78

T;T;T

MetaRNN

Benign

0.022

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.2

.;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.019

.;D;D

Sift4G

Uncertain

0.025

D;D;D

Polyphen

0.35, 0.21

.;B;B

Vest4

0.31

MVP

0.45

MPC

0.44

ClinPred

0.012

GERP RS

3.1

Varity_R

0.23

gMVP

0.67

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

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