chr10-73914121-C-T

Position:

chr10-73914121-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002658.6(PLAU):c.822C>T(p.Asn274=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,432 control chromosomes in the GnomAD database, including 21,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1608 hom., cov: 33)

Exomes 𝑓: 0.16 ( 20183 hom. )

Consequence

PLAU
NM_002658.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.09

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 10-73914121-C-T is Benign according to our data. Variant chr10-73914121-C-T is described in ClinVar as [Benign]. Clinvar id is 300756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 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.822C>T	p.Asn274=	synonymous_variant	8/11	ENST00000372764.4
C10orf55	NR_160938.1 linkuse as main transcript	n.269-1046G>A		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.822C>T	p.Asn274=	synonymous_variant	8/11	1	NM_002658.6	P1	P00749-1
C10orf55	ENST00000409178.5 linkuse as main transcript	n.269-1046G>A		intron_variant, non_coding_transcript_variant		1
PLAU	ENST00000446342.5 linkuse as main transcript	c.771C>T	p.Asn257=	synonymous_variant	7/10	2			P00749-2

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19827

AN:

152132

Hom.:

1609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0619

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.0899

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.166

AC:

41745

AN:

250806

Hom.:

4082

AF XY:

0.174

AC XY:

23557

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.0655

Gnomad AMR exome

AF:

0.0969

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.312

Gnomad SAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.159

AC:

232687

AN:

1461182

Hom.:

20183

Cov.:

AF XY:

0.163

AC XY:

118366

AN XY:

726930

show subpopulations

Gnomad4 AFR exome

AF:

0.0612

Gnomad4 AMR exome

AF:

0.0956

Gnomad4 ASJ exome

AF:

0.269

Gnomad4 EAS exome

AF:

0.321

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.130

AC:

19826

AN:

152250

Hom.:

1608

Cov.:

AF XY:

0.130

AC XY:

9701

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0618

Gnomad4 AMR

AF:

0.0899

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.308

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.150

Hom.:

2187

Bravo

AF:

0.125

Asia WGS

AF:

0.242

AC:

843

AN:

3478

EpiCase

AF:

0.153

EpiControl

AF:

0.152

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Quebec platelet disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.19

DANN

Benign

0.90

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