chr10-73913973-C-T

Position:

chr10-73913973-C-T

Variant summary

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

The NM_002658.6(PLAU):c.681-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,610,644 control chromosomes in the GnomAD database, including 228,116 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19388 hom., cov: 32)

Exomes 𝑓: 0.52 ( 208728 hom. )

Consequence

PLAU
NM_002658.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005973

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.341

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-73913973-C-T is Benign according to our data. Variant chr10-73913973-C-T is described in ClinVar as [Benign]. Clinvar id is 300752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-73913973-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 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.681-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000372764.4
C10orf55	NR_160938.1 linkuse as main transcript	n.269-898G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
PLAU	ENST00000372764.4 linkuse as main transcript	c.681-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_002658.6	P1	P00749-1
C10orf55	ENST00000409178.5 linkuse as main transcript	n.269-898G>A	intron_variant, non_coding_transcript_variant	1
PLAU	ENST00000446342.5 linkuse as main transcript	c.630-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2			P00749-2

Frequencies

GnomAD3 genomes

AF:

0.496

AC:

75330

AN:

151952

Hom.:

19381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.586

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.566

Gnomad OTH

AF:

0.565

GnomAD3 exomes

AF:

0.453

AC:

113615

AN:

251014

Hom.:

29051

AF XY:

0.457

AC XY:

62021

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.314

Gnomad ASJ exome

AF:

0.574

Gnomad EAS exome

AF:

0.102

Gnomad SAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.468

Gnomad NFE exome

AF:

0.574

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.523

AC:

763207

AN:

1458574

Hom.:

208728

Cov.:

AF XY:

0.519

AC XY:

376794

AN XY:

725790

show subpopulations

Gnomad4 AFR exome

AF:

0.455

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.579

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.310

Gnomad4 FIN exome

AF:

0.466

Gnomad4 NFE exome

AF:

0.566

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

AF:

0.496

AC:

75363

AN:

152070

Hom.:

19388

Cov.:

AF XY:

0.488

AC XY:

36296

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.457

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.586

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.475

Gnomad4 NFE

AF:

0.566

Gnomad4 OTH

AF:

0.560

Alfa

AF:

0.561

Hom.:

32305

Bravo

AF:

0.495

Asia WGS

AF:

0.215

AC:

748

AN:

3478

EpiCase

AF:

0.586

EpiControl

AF:

0.597

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Quebec platelet disorder

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.5

DANN

Benign

0.79

BranchPoint Hunter

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000060

dbscSNV1_RF

Benign

0.0020

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