10-73911404-G-T

Position:

• chr10-73911404-G-T

Variant summary

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

The NM_002658.6(PLAU):​c.-31-121G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,050,712 control chromosomes in the GnomAD database, including 144,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19413 hom., cov: 33)
  • Exomes 𝑓: 0.51 (125486 hom.)
• Consequence: PLAU NM_002658.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.266

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=-0.79).
• BP6: Variant 10-73911404-G-T is Benign according to our data. Variant chr10-73911404-G-T is described in ClinVar as [Benign]. Clinvar id is 1237018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAU	NM_002658.6	c.-31-121G>T		intron_variant		ENST00000372764.4	NP_002649.2
C10orf55	NR_160938.1	n.1078C>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAU	ENST00000372764.4	c.-31-121G>T		intron_variant		1	NM_002658.6	ENSP00000361850	P1
C10orf55	ENST00000409178.5	n.1078C>A		non_coding_transcript_exon_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75387 AN: 151982 Hom.: 19406 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.566

GnomAD4 exome AF: 0.514 AC: 461656 AN: 898612 Hom.: 125486 Cov.: 12 AF XY: 0.508 AC XY: 234557 AN XY: 461572

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.496 AC: 75420 AN: 152100 Hom.: 19413 Cov.: 33 AF XY: 0.488 AC XY: 36311 AN XY: 74356

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.561

Alfa AF: 0.520 Hom.: 6429

Bravo AF: 0.496

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.3
DANN	Benign	0.49

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: rs1916341; hg19: chr10-75671162;