10-73912619-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002658.6(PLAU):c.193+297_193+298insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,534 control chromosomes in the GnomAD database, including 19,022 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (19022 hom., cov: 31)
• Consequence: PLAU NM_002658.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.306

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 -10 ACMG points.

• BP6: Variant 10-73912619-G-GT is Benign according to our data. Variant chr10-73912619-G-GT is described in ClinVar as [Benign]. Clinvar id is 1287381.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAU	NM_002658.6	c.193+297_193+298insT		intron_variant		ENST00000372764.4
C10orf55	NR_160938.1	n.302-336_302-335insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAU	ENST00000372764.4	c.193+297_193+298insT		intron_variant		1	NM_002658.6	P1
C10orf55	ENST00000409178.5	n.302-336_302-335insA		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74535 AN: 151412 Hom.: 19016 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.562

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.492 AC: 74564 AN: 151534 Hom.: 19022 Cov.: 31 AF XY: 0.485 AC XY: 35873 AN XY: 74024

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.558

Alfa AF: 0.130 Hom.: 499

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs112784885; hg19: chr10-75672377;