19-43665345-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002659.4(PLAUR):c.281G>A(p.Gly94Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,613,966 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00088 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0014 (3 hom.)
• Consequence: PLAUR NM_002659.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.718

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 19-43665345-C-T is Benign according to our data. Variant chr19-43665345-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049622.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAUR	NM_002659.4	c.281G>A	p.Gly94Glu	missense_variant	3/7	ENST00000340093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAUR	ENST00000340093.8	c.281G>A	p.Gly94Glu	missense_variant	3/7	1	NM_002659.4	P1

Frequencies

GnomAD3 genomes AF: 0.000882 AC: 134 AN: 151976 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000411

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

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: 0.00144

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00101 AC: 253 AN: 251486 Hom.: 1 AF XY: 0.00107 AC XY: 146 AN XY: 135920

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00164

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00135 AC: 1974 AN: 1461872 Hom.: 3 Cov.: 31 AF XY: 0.00133 AC XY: 964 AN XY: 727242

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00165

Gnomad4 OTH exome AF: 0.000960

GnomAD4 genome AF: 0.000881 AC: 134 AN: 152094 Hom.: 0 Cov.: 30 AF XY: 0.000821 AC XY: 61 AN XY: 74334

Gnomad4 AFR AF: 0.000410

Gnomad4 AMR AF: 0.00125

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00165 Hom.: 0

Bravo AF: 0.00107

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.000881 AC: 107

EpiCase AF: 0.00185

EpiControl AF: 0.00225

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PLAUR-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 28, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	12
Dann	Benign	0.64
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.75	T;T;T;T;T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.015	T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L;.;L;L;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N;.;N;N;.;.;.
REVEL	Benign	0.12
Sift	Benign	0.19	T;.;T;T;.;.;.
Sift4G	Benign	0.19	T;T;T;T;T;.;.
Polyphen		0.017	B;.;B;B;.;.;.
Vest4		0.21
MVP		0.35
MPC		0.21
ClinPred		0.0050	T
GERP RS		-0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.52		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.52		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs150986089; hg19: chr19-44169497;