chr19-43665373-T-C

Variant names:

• chr19-43665373-T-C
• NM_002659.4:c.253A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002659.4(PLAUR):​c.253A>G​(p.Ile85Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I85T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: PLAUR NM_002659.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23902708).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002659.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	NM_002659.4	MANE Select	c.253A>G	p.Ile85Val	missense	Exon 3 of 7	NP_002650.1	Q03405-1
	PLAUR	NM_001005377.3		c.253A>G	p.Ile85Val	missense	Exon 3 of 6	NP_001005377.1	Q03405-3
	PLAUR	NM_001301037.2		c.253A>G	p.Ile85Val	missense	Exon 3 of 6	NP_001287966.1	M0R1I2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	ENST00000340093.8	TSL:1 MANE Select	c.253A>G	p.Ile85Val	missense	Exon 3 of 7	ENSP00000339328.3	Q03405-1
	PLAUR	ENST00000221264.8	TSL:1	c.253A>G	p.Ile85Val	missense	Exon 3 of 6	ENSP00000221264.3	Q03405-3
	PLAUR	ENST00000601723.5	TSL:1	c.253A>G	p.Ile85Val	missense	Exon 3 of 6	ENSP00000471881.1	M0R1I2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.12
Sift	Benign	0.23	T
Sift4G	Benign	0.29	T
Polyphen		0.016	B
Vest4		0.14
MutPred		0.73		Gain of disorder (P = 0.0601)
MVP		0.33
MPC		0.12
ClinPred		0.11	T
GERP RS		2.8
Varity_R		0.14
gMVP		0.31
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

hg19: chr19-44169525;