10-73911598-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145031.3(PLAU):c.-294G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

PLAU
NM_001145031.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.995

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: 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=0.24634475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145031.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLAU	NM_002658.6	MANE Select	c.43G>A	p.Val15Met	missense	Exon 2 of 11	NP_002649.2	P00749-1
PLAU	NM_001145031.3		c.-294G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001138503.2	P00749-2
PLAU	NM_001319191.2		c.-188G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001306120.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLAU	ENST00000372764.4	TSL:1 MANE Select	c.43G>A	p.Val15Met	missense	Exon 2 of 11	ENSP00000361850.3	P00749-1
C10orf55	ENST00000409178.5	TSL:1	n.884C>T		non_coding_transcript_exon	Exon 5 of 5
PLAU	ENST00000446342.5	TSL:2	c.-294G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	ENSP00000388474.1	P00749-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.048

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.63

M_CAP

Benign

0.060

MetaRNN

Benign

0.25

MetaSVM

Uncertain

-0.21

PhyloP100

0.99

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.16

REVEL

Benign

0.25

Sift

Uncertain

0.029

Sift4G

Pathogenic

0.0

Vest4

0.40

MutPred

0.28

Loss of sheet (P = 0.0315)

MVP

0.94

MPC

0.28

ClinPred

0.67

GERP RS

2.8

PromoterAI

0.0094

Neutral

(source)

gMVP

0.44

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over