rs399145

Variant names:

• chr19-43665370-T-C
• rs399145
• NM_002659.4:c.256A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002659.4(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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (207 hom., cov: 30)
  • Exomes 𝑓: 0.0030 (206 hom.)
• Consequence: PLAUR NM_002659.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.761
• Publications: 12 publications found

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]

ENSG00000308028 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLAUR	NM_002659.4	c.256A>G	p.Thr86Ala	missense_variant	Exon 3 of 7	ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.256A>G	p.Thr86Ala	missense_variant	Exon 3 of 7	1	NM_002659.4	ENSP00000339328.3

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

GnomAD2 exomes AF: 0.00823 AC: 2071 AN: 251490 AF XY: 0.00575

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 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

African (AFR) AF: 0.0985 AC: 3298 AN: 33474

American (AMR) AF: 0.00707 AC: 316 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00788 AC: 206 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5768

European-Non Finnish (NFE) AF: 0.000206 AC: 229 AN: 1111978

Other (OTH) AF: 0.00588 AC: 355 AN: 60394

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

African (AFR) AF: 0.103 AC: 4256 AN: 41414

American (AMR) AF: 0.0123 AC: 188 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 67976

Other (OTH) AF: 0.0247 AC: 52 AN: 2108

Alfa AF: 0.0115 Hom.: 180

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;.;.;.;.
PhyloP100		0.76
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs399145; hg19: chr19-44169522;