rs399145

Positions:

• chr19-43665370-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000340093.8(PLAUR):​c.256A>G​(p.Thr86Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,613,834 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.030 (207 hom., cov: 30)
  • Exomes 𝑓: 0.0030 (206 hom.)
• Consequence: PLAUR ENST00000340093.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.761

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019513369).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.256A>G	p.Thr86Ala	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	c.256A>G	p.Thr86Ala	missense_variant	3/7	1	NM_002659.4	ENSP00000339328	P1

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4558 AN: 151868 Hom.: 209 Cov.: 30

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.00823 AC: 2071 AN: 251490 Hom.: 101 AF XY: 0.00575 AC XY: 782 AN XY: 135920

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00596

Gnomad ASJ exome AF: 0.00764

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000325

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00303 AC: 4434 AN: 1461850 Hom.: 206 Cov.: 31 AF XY: 0.00254 AC XY: 1848 AN XY: 727228

Gnomad4 AFR exome AF: 0.0985

Gnomad4 AMR exome AF: 0.00707

Gnomad4 ASJ exome AF: 0.00788

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000206

Gnomad4 OTH exome AF: 0.00588

GnomAD4 genome AF: 0.0300 AC: 4559 AN: 151984 Hom.: 207 Cov.: 30 AF XY: 0.0284 AC XY: 2111 AN XY: 74292

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.00594 Hom.: 59

Bravo AF: 0.0342

ESP6500AA AF: 0.105 AC: 461

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0103 AC: 1251

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.028	.;T;T;.;T;.;.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.74	T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0020	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;N;N;.;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.29	N;.;N;N;.;.;.;.
REVEL	Benign	0.086
Sift	Benign	0.23	T;.;T;T;.;.;.;.
Sift4G	Benign	0.11	T;T;T;T;T;.;.;.
Polyphen		0.0030	B;.;B;B;.;.;.;.
Vest4		0.14
MPC		0.13
ClinPred		0.0087	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.37

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

Other links and lift over

dbSNP: rs399145; hg19: chr19-44169522;