10-73916706-C-T

Position:

• chr10-73916706-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000372764.4(PLAU):​c.*141C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 701,926 control chromosomes in the GnomAD database, including 99,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20132 hom., cov: 33)
  • Exomes 𝑓: 0.52 (79066 hom.)
• Consequence: PLAU ENST00000372764.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0110

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]

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-73916706-C-T is Benign according to our data. Variant chr10-73916706-C-T is described in ClinVar as [Benign]. Clinvar id is 300765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAU	NM_002658.6	c.*141C>T		3_prime_UTR_variant	11/11	ENST00000372764.4	NP_002649.2
C10orf55	NR_160938.1	n.146-65G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAU	ENST00000372764.4	c.*141C>T		3_prime_UTR_variant	11/11	1	NM_002658.6	ENSP00000361850	P1
C10orf55	ENST00000409178.5	n.146-65G>A		intron_variant, non_coding_transcript_variant		1
PLAU	ENST00000446342.5	c.*141C>T		3_prime_UTR_variant	10/10	2		ENSP00000388474

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76748 AN: 151990 Hom.: 20128 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.517 AC: 284423 AN: 549818 Hom.: 79066 Cov.: 7 AF XY: 0.511 AC XY: 145491 AN XY: 284984

Gnomad4 AFR exome AF: 0.472

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.599

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.460

Gnomad4 NFE exome AF: 0.585

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.505 AC: 76778 AN: 152108 Hom.: 20132 Cov.: 33 AF XY: 0.497 AC XY: 36952 AN XY: 74336

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.574

Alfa AF: 0.575 Hom.: 23800

Bravo AF: 0.505

Asia WGS AF: 0.218 AC: 759 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Quebec platelet disorder Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs4065; hg19: chr10-75676464;