chr19-43655510-T-C

Variant names:

• chr19-43655510-T-C
• rs138306315
• NM_002659.4:c.536A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_002659.4(PLAUR):​c.536A>G​(p.Asn179Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,614,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: PLAUR NM_002659.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.915
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011186212).
• BP6: Variant 19-43655510-T-C is Benign according to our data. Variant chr19-43655510-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 741417.Status of the report is criteria_provided_single_submitter, 1 stars.

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.536A>G	p.Asn179Ser	missense	Exon 5 of 7	NP_002650.1	Q03405-1
	PLAUR	NM_001301037.2		c.536A>G	p.Asn179Ser	missense	Exon 5 of 6	NP_001287966.1	M0R1I2
	PLAUR	NM_001005376.3		c.536A>G	p.Asn179Ser	missense	Exon 5 of 7	NP_001005376.1	Q03405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	ENST00000340093.8	TSL:1 MANE Select	c.536A>G	p.Asn179Ser	missense	Exon 5 of 7	ENSP00000339328.3	Q03405-1
	PLAUR	ENST00000601723.5	TSL:1	c.536A>G	p.Asn179Ser	missense	Exon 5 of 6	ENSP00000471881.1	M0R1I2
	PLAUR	ENST00000339082.7	TSL:1	c.536A>G	p.Asn179Ser	missense	Exon 5 of 7	ENSP00000342049.2	Q03405-2

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000243 AC: 61 AN: 251464 AF XY: 0.000162

Gnomad AFR exome AF: 0.00283

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000105 AC: 153 AN: 1461872 Hom.: 1 Cov.: 31 AF XY: 0.0000963 AC XY: 70 AN XY: 727236

African (AFR) AF: 0.00263 AC: 88 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

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

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111996

Other (OTH) AF: 0.000248 AC: 15 AN: 60396

GnomAD4 genome AF: 0.000926 AC: 141 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000819 AC XY: 61 AN XY: 74474

African (AFR) AF: 0.00308 AC: 128 AN: 41584

American (AMR) AF: 0.000523 AC: 8 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000515 Hom.: 0

Bravo AF: 0.00112

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00431 AC: 19

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000305 AC: 37

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.6
DANN	Benign	0.43
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.92
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.012
Sift	Benign	0.67	T
Sift4G	Benign	0.50	T
Polyphen		0.0020	B
Vest4		0.11
MVP		0.18
MPC		0.099
ClinPred		0.0015	T
GERP RS		1.4
Varity_R		0.059
gMVP		0.14
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs138306315; hg19: chr19-44159662;