chr8-42176001-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2
The NM_000930.5(PLAT):c.1681C>T(p.Arg561Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,613,954 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0058 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00062 ( 15 hom. )
Consequence
PLAT
NM_000930.5 stop_gained
NM_000930.5 stop_gained
Scores
1
1
5
Clinical Significance
Conservation
PhyloP100: 0.301
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 Benign. Variant got -8 ACMG points.
PM4
?
Stoplost variant in NM_000930.5 Downstream stopcodon found after 52 codons.
BP6
?
Variant 8-42176001-G-A is Benign according to our data. Variant chr8-42176001-G-A is described in ClinVar as [Benign]. Clinvar id is 716389.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00581 (885/152286) while in subpopulation AFR AF= 0.0202 (838/41556). AF 95% confidence interval is 0.019. There are 6 homozygotes in gnomad4. There are 407 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLAT | NM_000930.5 | c.1681C>T | p.Arg561Ter | stop_gained | 14/14 | ENST00000220809.9 | |
PLAT | NM_033011.4 | c.1543C>T | p.Arg515Ter | stop_gained | 13/13 | ||
PLAT | NM_001319189.2 | c.1414C>T | p.Arg472Ter | stop_gained | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLAT | ENST00000220809.9 | c.1681C>T | p.Arg561Ter | stop_gained | 14/14 | 1 | NM_000930.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00583 AC: 887AN: 152168Hom.: 6 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
887
AN:
152168
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00154 AC: 388AN: 251166Hom.: 6 AF XY: 0.00109 AC XY: 148AN XY: 135760
GnomAD3 exomes
AF:
AC:
388
AN:
251166
Hom.:
AF XY:
AC XY:
148
AN XY:
135760
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000624 AC: 912AN: 1461668Hom.: 15 Cov.: 31 AF XY: 0.000538 AC XY: 391AN XY: 727132
GnomAD4 exome
AF:
AC:
912
AN:
1461668
Hom.:
Cov.:
31
AF XY:
AC XY:
391
AN XY:
727132
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00581 AC: 885AN: 152286Hom.: 6 Cov.: 32 AF XY: 0.00547 AC XY: 407AN XY: 74448
GnomAD4 genome
?
AF:
AC:
885
AN:
152286
Hom.:
Cov.:
32
AF XY:
AC XY:
407
AN XY:
74448
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
91
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
218
Asia WGS
AF:
AC:
4
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
D;D;D;D;N;N;N
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at