Genetic Variant PLAT:p.Arg164Gly (chr8-42187447-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000930.5(PLAT):c.490C>G(p.Arg164Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PLAT
NM_000930.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Publications

0 publications found

Variant links:

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

PLAT links:

ENSG00000304994 (HGNC:):

ENSG00000304994 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34313175).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000930.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLAT	NM_000930.5	MANE Select	c.490C>G	p.Arg164Gly	missense	Exon 6 of 14	NP_000921.1
PLAT	NM_033011.4		c.352C>G	p.Arg118Gly	missense	Exon 5 of 13	NP_127509.1
PLAT	NM_001319189.2		c.364+459C>G		intron	N/A	NP_001306118.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLAT	ENST00000220809.9	TSL:1 MANE Select	c.490C>G	p.Arg164Gly	missense	Exon 6 of 14	ENSP00000220809.4
PLAT	ENST00000352041.7	TSL:1	c.352C>G	p.Arg118Gly	missense	Exon 5 of 13	ENSP00000270188.6
PLAT	ENST00000521647.1	TSL:1	n.710C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.85

M_CAP

Benign

0.050

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.3

PhyloP100

1.1

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.13

Sift

Benign

0.085

Sift4G

Benign

0.16

Polyphen

0.51

Vest4

0.49

MutPred

0.60

Gain of ubiquitination at K159 (P = 0.034)

MVP

0.68

MPC

0.73

ClinPred

0.95

GERP RS

1.9

Varity_R

0.51

gMVP

0.47

Mutation Taster

=65/35

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over