Variant 19-43665450-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000340093.8(PLAUR):c.176A>T(p.Glu59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,612,922 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

PLAUR
ENST00000340093.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.35

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAUR	NM_002659.4 linkuse as main transcript	c.176A>T	p.Glu59Val	missense_variant	3/7	ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8 linkuse as main transcript	c.176A>T	p.Glu59Val	missense_variant	3/7	1	NM_002659.4	ENSP00000339328	P1	Q03405-1

Frequencies

GnomAD3 genomes

AF:

0.0000728

AC:

AN:

151072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251446

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000166

AC:

242

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000199

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.0000728

AC:

AN:

151072

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

73638

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.176A>T (p.E59V) alteration is located in exon 3 (coding exon 3) of the PLAUR gene. This alteration results from a A to T substitution at nucleotide position 176, causing the glutamic acid (E) at amino acid position 59 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.11

.;T;T;.;T;.;.;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.032

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.82

T;T;T;T;T;T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.44

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.8

L;.;L;L;.;.;.;.

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-4.7

D;.;D;D;.;.;.;.

REVEL

Uncertain

0.51

Sift

Uncertain

0.0030

D;.;D;D;.;.;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;.;.;.

Polyphen

0.68

P;.;D;D;.;.;.;.

Vest4

0.38

MVP

0.72

MPC

0.16

ClinPred

0.44

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

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