rs1058720

Variant names:

• chr8-42187436-G-A
• rs1058720
• NM_000930.5:c.501C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-42187436-G-A
• chr8-42187436-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000930.5(PLAT):​c.501C>T​(p.Asp167Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,599,912 control chromosomes in the GnomAD database, including 252,845 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (20670 hom., cov: 34)
  • Exomes 𝑓: 0.57 (232175 hom.)
• Consequence: PLAT NM_000930.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 24 publications found

Genes affected

PLAT (HGNC:9051): (plasminogen activator, tissue type) This gene encodes tissue-type plasminogen activator, a secreted serine protease that converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. The encoded preproprotein is proteolytically processed by plasmin or trypsin to generate heavy and light chains. These chains associate via disulfide linkages to form the heterodimeric enzyme. This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding, while decreased activity leads to hypofibrinolysis, which can result in thrombosis or embolism. Alternative splicing of this gene results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

PLAT Gene-Disease associations (from GenCC):

• thrombophilia, familial, due to decreased release of tissue plasminogen activator

  Inheritance: AR, AD Classification: MODERATE, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen

ENSG00000304994 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.266 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAT	NM_000930.5	c.501C>T	p.Asp167Asp	synonymous_variant	Exon 6 of 14	ENST00000220809.9	NP_000921.1
PLAT	NM_033011.4	c.363C>T	p.Asp121Asp	synonymous_variant	Exon 5 of 13		NP_127509.1
PLAT	NM_001319189.2	c.364+470C>T		intron_variant	Intron 5 of 11		NP_001306118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAT	ENST00000220809.9	c.501C>T	p.Asp167Asp	synonymous_variant	Exon 6 of 14	1	NM_000930.5	ENSP00000220809.4

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78404 AN: 152110 Hom.: 20674 Cov.: 34

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.544

GnomAD2 exomes AF: 0.550 AC: 133028 AN: 241960 AF XY: 0.553

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.497

Gnomad EAS exome AF: 0.522

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.565 AC: 818148 AN: 1447684 Hom.: 232175 Cov.: 48 AF XY: 0.564 AC XY: 406534 AN XY: 720290

African (AFR) AF: 0.392 AC: 13113 AN: 33420

American (AMR) AF: 0.578 AC: 25731 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12869 AN: 26012

East Asian (EAS) AF: 0.547 AC: 21680 AN: 39644

South Asian (SAS) AF: 0.554 AC: 47600 AN: 85916

European-Finnish (FIN) AF: 0.581 AC: 24881 AN: 42820

Middle Eastern (MID) AF: 0.482 AC: 2772 AN: 5752

European-Non Finnish (NFE) AF: 0.573 AC: 636142 AN: 1109462

Other (OTH) AF: 0.555 AC: 33360 AN: 60126

GnomAD4 genome AF: 0.515 AC: 78430 AN: 152228 Hom.: 20670 Cov.: 34 AF XY: 0.516 AC XY: 38410 AN XY: 74420

African (AFR) AF: 0.398 AC: 16517 AN: 41534

American (AMR) AF: 0.544 AC: 8329 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1714 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2699 AN: 5174

South Asian (SAS) AF: 0.567 AC: 2739 AN: 4832

European-Finnish (FIN) AF: 0.573 AC: 6068 AN: 10586

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38572 AN: 68010

Other (OTH) AF: 0.539 AC: 1140 AN: 2114

Alfa AF: 0.544 Hom.: 56992

Bravo AF: 0.509

Asia WGS AF: 0.522 AC: 1816 AN: 3478

EpiCase AF: 0.564

EpiControl AF: 0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.073
DANN	Benign	0.32
PhyloP100		-0.27
Mutation Taster		=98/2	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: rs1058720; hg19: chr8-42044954; COSMIC: COSV54274776; COSMIC: COSV54274776;