rs2227567

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002658.6(PLAU):c.691A>C(p.Lys231Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00978 in 1,613,688 control chromosomes in the GnomAD database, including 1,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 503 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 507 hom. )

Consequence

PLAU
NM_002658.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.794

Publications

13 publications found

Variant links:

Genes affected

PLAU (HGNC:9052): (plasminogen activator, urokinase) This gene encodes a secreted serine protease that converts plasminogen to plasmin. The encoded preproprotein is proteolytically processed to generate A and B polypeptide chains. These chains associate via a single disulfide bond to form the catalytically inactive high molecular weight urokinase-type plasminogen activator (HMW-uPA). HMW-uPA can be further processed into the catalytically active low molecular weight urokinase-type plasminogen activator (LMW-uPA). This low molecular weight form does not bind to the urokinase-type plasminogen activator receptor. Mutations in this gene may be associated with Quebec platelet disorder and late-onset Alzheimer's disease. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

PLAU links:

C10orf55 (HGNC:31008): (chromosome 10 putative open reading frame 55) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

C10orf55 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001355797).

BP6

Variant 10-73913990-A-C is Benign according to our data. Variant chr10-73913990-A-C is described in ClinVar as Benign. ClinVar VariationId is 300753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002658.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLAU	NM_002658.6	MANE Select	c.691A>C	p.Lys231Gln	missense	Exon 8 of 11	NP_002649.2
PLAU	NM_001441154.1		c.691A>C	p.Lys231Gln	missense	Exon 9 of 12	NP_001428083.1
PLAU	NM_001441155.1		c.691A>C	p.Lys231Gln	missense	Exon 8 of 11	NP_001428084.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLAU	ENST00000372764.4	TSL:1 MANE Select	c.691A>C	p.Lys231Gln	missense	Exon 8 of 11	ENSP00000361850.3
C10orf55	ENST00000409178.5	TSL:1	n.269-915T>G		intron	N/A
PLAU	ENST00000446342.5	TSL:2	c.640A>C	p.Lys214Gln	missense	Exon 7 of 10	ENSP00000388474.1

Frequencies

GnomAD3 genomes

AF:

0.0449

AC:

6834

AN:

152170

Hom.:

498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0215

GnomAD2 exomes

AF:

0.0149

AC:

3740

AN:

251332

AF XY:

0.0124

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.00755

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00611

AC:

8928

AN:

1461400

Hom.:

507

Cov.:

AF XY:

0.00613

AC XY:

4458

AN XY:

727026

show subpopulations

African (AFR)

AF:

0.157

AC:

5268

AN:

33450

American (AMR)

AF:

0.00850

AC:

380

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00165

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0247

AC:

2134

AN:

86244

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.0101

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000246

AC:

274

AN:

1111606

Other (OTH)

AF:

0.0125

AC:

752

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

450

900

1350

1800

2250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0450

AC:

6855

AN:

152288

Hom.:

503

Cov.:

AF XY:

0.0437

AC XY:

3255

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.153

AC:

6334

AN:

41534

American (AMR)

AF:

0.0195

AC:

299

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0269

AC:

130

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68018

Other (OTH)

AF:

0.0213

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

301

602

903

1204

1505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0143

Hom.:

366

Bravo

AF:

0.0516

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.149

AC:

657

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0183

AC:

2217

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Quebec platelet disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.22

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.19

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.98

PhyloP100

-0.79

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.24

REVEL

Benign

0.0060

Sift

Benign

0.40

Sift4G

Benign

0.61

Polyphen

0.0020

Vest4

0.071

MPC

0.30

ClinPred

0.0023

GERP RS

-5.3

gMVP

0.39

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over