19-43648936-A-C

Position:

• chr19-43648936-A-C

Variant summary

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

The ENST00000340093.8(PLAUR):​c.962T>G​(p.Leu321Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PLAUR ENST00000340093.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

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 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	c.962T>G	p.Leu321Arg	missense_variant	7/7	ENST00000340093.8	NP_002650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAUR	ENST00000340093.8	c.962T>G	p.Leu321Arg	missense_variant	7/7	1	NM_002659.4	ENSP00000339328	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.962T>G (p.L321R) alteration is located in exon 7 (coding exon 7) of the PLAUR gene. This alteration results from a T to G substitution at nucleotide position 962, causing the leucine (L) at amino acid position 321 to be replaced by an arginine (R). 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	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Benign	0.82
DEOGEN2	Benign	0.15	T;T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.1	.;N;D
REVEL	Benign	0.28
Sift	Uncertain	0.0090	.;D;D
Sift4G	Uncertain	0.051	T;T;T
Polyphen		0.95, 0.97	.;P;D
Vest4		0.82
MutPred		0.64		.;Gain of MoRF binding (P = 0.007);.;
MVP		0.067
MPC		0.33
ClinPred		0.23	T
GERP RS		1.6
Varity_R		0.10
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-44153088;