8-42176099-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000930.5(PLAT):​c.1583T>G​(p.Val528Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PLAT
NM_000930.5 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLATNM_000930.5 linkc.1583T>G p.Val528Gly missense_variant Exon 14 of 14 ENST00000220809.9 NP_000921.1 P00750-1
PLATNM_033011.4 linkc.1445T>G p.Val482Gly missense_variant Exon 13 of 13 NP_127509.1 P00750-3
PLATNM_001319189.2 linkc.1316T>G p.Val439Gly missense_variant Exon 12 of 12 NP_001306118.1 P00750B4DN26

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLATENST00000220809.9 linkc.1583T>G p.Val528Gly missense_variant Exon 14 of 14 1 NM_000930.5 ENSP00000220809.4 P00750-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250922
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135628
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461680
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1583T>G (p.V528G) alteration is located in exon 14 (coding exon 13) of the PLAT gene. This alteration results from a T to G substitution at nucleotide position 1583, causing the valine (V) at amino acid position 528 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.90
D;D;.;.;D;.
Eigen
Benign
0.096
Eigen_PC
Benign
0.0060
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.82
.;T;T;T;T;T
M_CAP
Uncertain
0.23
D
MetaRNN
Uncertain
0.63
D;D;D;D;D;D
MetaSVM
Uncertain
0.36
D
MutationAssessor
Uncertain
2.1
M;M;.;.;.;.
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-3.3
D;D;D;D;D;D
REVEL
Pathogenic
0.69
Sift
Benign
0.082
T;T;D;D;T;D
Sift4G
Benign
0.20
T;T;T;T;T;T
Polyphen
0.97
D;D;D;.;D;D
Vest4
0.44
MVP
0.97
MPC
0.75
ClinPred
0.96
D
GERP RS
4.5
Varity_R
0.58
gMVP
0.82

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370723642; hg19: chr8-42033617; API