10-73909255-T-C

Position:

• chr10-73909255-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000481390.5(PLAU):​c.-71T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,062 control chromosomes in the GnomAD database, including 39,923 homozygotes. 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 0.72 (39920 hom., cov: 31)
  • Exomes 𝑓: 0.63 (3 hom.)
• Consequence: PLAU ENST00000481390.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAU	XM_011539866.3	c.-71T>C		5_prime_UTR_variant	1/11		XP_011538168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAU	ENST00000481390.5	c.-71T>C		5_prime_UTR_variant	1/5	2		ENSP00000474318.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109234 AN: 151928 Hom.: 39887 Cov.: 31

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.625 AC: 10 AN: 16 Hom.: 3 Cov.: 0 AF XY: 0.500 AC XY: 6 AN XY: 12

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.719 AC: 109307 AN: 152046 Hom.: 39920 Cov.: 31 AF XY: 0.709 AC XY: 52686 AN XY: 74310

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.753

Alfa AF: 0.701 Hom.: 4036

Bravo AF: 0.722

Asia WGS AF: 0.526 AC: 1832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2459449; hg19: chr10-75669013;