NM_002658.6:c.194-207A>G

Variant names:

• chr10-73912717-A-G
• rs2227560
• NM_002658.6:c.194-207A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002658.6(PLAU):​c.194-207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 151,836 control chromosomes in the GnomAD database, including 40,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.73 (40722 hom., cov: 29)
• Consequence: PLAU NM_002658.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.429
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 10-73912717-A-G is Benign according to our data. Variant chr10-73912717-A-G is described in ClinVar as Benign. ClinVar VariationId is 1183359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002658.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAU	NM_002658.6	MANE Select	c.194-207A>G		intron	N/A	NP_002649.2	P00749-1
	PLAU	NM_001441154.1		c.194-207A>G		intron	N/A	NP_001428083.1
	PLAU	NM_001441155.1		c.194-207A>G		intron	N/A	NP_001428084.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAU	ENST00000372764.4	TSL:1 MANE Select	c.194-207A>G		intron	N/A	ENSP00000361850.3	P00749-1
	C10orf55	ENST00000409178.5	TSL:1	n.301+326T>C		intron	N/A
	PLAU	ENST00000894723.1		c.194-207A>G		intron	N/A	ENSP00000564782.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110193 AN: 151718 Hom.: 40688 Cov.: 29

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.726 AC: 110269 AN: 151836 Hom.: 40722 Cov.: 29 AF XY: 0.716 AC XY: 53142 AN XY: 74198

African (AFR) AF: 0.806 AC: 33361 AN: 41394

American (AMR) AF: 0.601 AC: 9150 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3114 AN: 3468

East Asian (EAS) AF: 0.482 AC: 2477 AN: 5144

South Asian (SAS) AF: 0.593 AC: 2858 AN: 4818

European-Finnish (FIN) AF: 0.627 AC: 6596 AN: 10522

Middle Eastern (MID) AF: 0.860 AC: 251 AN: 292

European-Non Finnish (NFE) AF: 0.739 AC: 50227 AN: 67948

Other (OTH) AF: 0.758 AC: 1596 AN: 2106

Alfa AF: 0.734 Hom.: 4733

Bravo AF: 0.730

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.36
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2227560; hg19: chr10-75672475;