10-73912117-G-A

Position:

• chr10-73912117-G-A

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.85+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 1,605,330 control chromosomes in the GnomAD database, including 5,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (352 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5322 hom.)
• Consequence: PLAU NM_002658.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.748

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=-0.78).
• BP6: Variant 10-73912117-G-A is Benign according to our data. Variant chr10-73912117-G-A is described in ClinVar as [Benign]. Clinvar id is 1240521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAU	NM_002658.6	c.85+49G>A		intron_variant		ENST00000372764.4	NP_002649.2
C10orf55	NR_160938.1	n.387-22C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAU	ENST00000372764.4	c.85+49G>A		intron_variant		1	NM_002658.6	ENSP00000361850	P1
C10orf55	ENST00000409178.5	n.387-22C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8729 AN: 152088 Hom.: 351 Cov.: 32

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.0580

GnomAD3 exomes AF: 0.0621 AC: 15241 AN: 245460 Hom.: 604 AF XY: 0.0654 AC XY: 8652 AN XY: 132308

Gnomad AFR exome AF: 0.0148

Gnomad AMR exome AF: 0.0329

Gnomad ASJ exome AF: 0.0519

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.0826

Gnomad FIN exome AF: 0.0482

Gnomad NFE exome AF: 0.0864

Gnomad OTH exome AF: 0.0592

GnomAD4 exome AF: 0.0806 AC: 117136 AN: 1453124 Hom.: 5322 Cov.: 33 AF XY: 0.0810 AC XY: 58464 AN XY: 721684

Gnomad4 AFR exome AF: 0.0134

Gnomad4 AMR exome AF: 0.0339

Gnomad4 ASJ exome AF: 0.0546

Gnomad4 EAS exome AF: 0.000404

Gnomad4 SAS exome AF: 0.0840

Gnomad4 FIN exome AF: 0.0466

Gnomad4 NFE exome AF: 0.0899

Gnomad4 OTH exome AF: 0.0732

GnomAD4 genome AF: 0.0574 AC: 8739 AN: 152206 Hom.: 352 Cov.: 32 AF XY: 0.0555 AC XY: 4132 AN XY: 74398

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0507

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0753

Gnomad4 FIN AF: 0.0441

Gnomad4 NFE AF: 0.0900

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0719 Hom.: 91

Bravo AF: 0.0543

Asia WGS AF: 0.0440 AC: 154 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	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.62

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: rs2227581; hg19: chr10-75671875;