Variant 10-73912117-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002658.6(PLAU):c.85+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 1,605,330 control chromosomes in the GnomAD database, including 5,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 352 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5322 hom. )

Consequence

PLAU
NM_002658.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.748

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 10-73912117-G-A is Benign according to our data. Variant chr10-73912117-G-A is described in ClinVar as [Benign]. Clinvar id is 1240521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAU	NM_002658.6 linkuse as main transcript	c.85+49G>A		intron_variant		ENST00000372764.4
C10orf55	NR_160938.1 linkuse as main transcript	n.387-22C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAU	ENST00000372764.4 linkuse as main transcript	c.85+49G>A		intron_variant		1	NM_002658.6	P1	P00749-1
C10orf55	ENST00000409178.5 linkuse as main transcript	n.387-22C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0574

AC:

8729

AN:

152088

Hom.:

351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0157

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.0536

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0742

Gnomad FIN

AF:

0.0441

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0900

Gnomad OTH

AF:

0.0580

GnomAD3 exomes

AF:

0.0621

AC:

15241

AN:

245460

Hom.:

604

AF XY:

0.0654

AC XY:

8652

AN XY:

132308

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.0329

Gnomad ASJ exome

AF:

0.0519

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0826

Gnomad FIN exome

AF:

0.0482

Gnomad NFE exome

AF:

0.0864

Gnomad OTH exome

AF:

0.0592

GnomAD4 exome

AF:

0.0806

AC:

117136

AN:

1453124

Hom.:

5322

Cov.:

AF XY:

0.0810

AC XY:

58464

AN XY:

721684

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.0339

Gnomad4 ASJ exome

AF:

0.0546

Gnomad4 EAS exome

AF:

0.000404

Gnomad4 SAS exome

AF:

0.0840

Gnomad4 FIN exome

AF:

0.0466

Gnomad4 NFE exome

AF:

0.0899

Gnomad4 OTH exome

AF:

0.0732

GnomAD4 genome

AF:

0.0574

AC:

8739

AN:

152206

Hom.:

352

Cov.:

AF XY:

0.0555

AC XY:

4132

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.0507

Gnomad4 ASJ

AF:

0.0536

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0753

Gnomad4 FIN

AF:

0.0441

Gnomad4 NFE

AF:

0.0900

Gnomad4 OTH

AF:

0.0588

Alfa

AF:

0.0719

Hom.:

Bravo

AF:

0.0543

Asia WGS

AF:

0.0440

AC:

154

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over