10-73911404-G-T

Variant names:

• chr10-73911404-G-T
• rs1916341
• NM_002658.6:c.-31-121G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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 -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 VariationId 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.

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.-31-121G>T		intron	N/A	NP_002649.2
	PLAU	NM_001441154.1		c.-31-121G>T		intron	N/A	NP_001428083.1
	PLAU	NM_001441155.1		c.-31-121G>T		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.-31-121G>T		intron	N/A	ENSP00000361850.3
	C10orf55	ENST00000409178.5	TSL:1	n.1078C>A		non_coding_transcript_exon	Exon 5 of 5
	PLAU	ENST00000894723.1		c.-152G>T		5_prime_UTR	Exon 1 of 10	ENSP00000564782.1

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

African (AFR) AF: 0.461 AC: 10239 AN: 22204

American (AMR) AF: 0.348 AC: 12128 AN: 34850

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 12720 AN: 21910

East Asian (EAS) AF: 0.107 AC: 3588 AN: 33566

South Asian (SAS) AF: 0.313 AC: 21464 AN: 68636

European-Finnish (FIN) AF: 0.466 AC: 15473 AN: 33174

Middle Eastern (MID) AF: 0.635 AC: 1989 AN: 3130

European-Non Finnish (NFE) AF: 0.567 AC: 362500 AN: 639488

Other (OTH) AF: 0.517 AC: 21555 AN: 41654

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

African (AFR) AF: 0.458 AC: 19017 AN: 41496

American (AMR) AF: 0.463 AC: 7080 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2034 AN: 3470

East Asian (EAS) AF: 0.115 AC: 595 AN: 5176

South Asian (SAS) AF: 0.295 AC: 1424 AN: 4834

European-Finnish (FIN) AF: 0.474 AC: 5014 AN: 10588

Middle Eastern (MID) AF: 0.593 AC: 172 AN: 290

European-Non Finnish (NFE) AF: 0.566 AC: 38439 AN: 67924

Other (OTH) AF: 0.561 AC: 1188 AN: 2116

Alfa AF: 0.525 Hom.: 8195

Bravo AF: 0.496

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.3
DANN	Benign	0.49
PhyloP100		-0.27
PromoterAI		-0.0074	Neutral
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: rs1916341; hg19: chr10-75671162;