8-42180291-T-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000930.5(PLAT):c.1173A>G(p.Lys391=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,614,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
PLAT
NM_000930.5 synonymous
NM_000930.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0160
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 8-42180291-T-C is Benign according to our data. Variant chr8-42180291-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 754595.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.016 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLAT | NM_000930.5 | c.1173A>G | p.Lys391= | synonymous_variant | 11/14 | ENST00000220809.9 | |
PLAT | NM_033011.4 | c.1035A>G | p.Lys345= | synonymous_variant | 10/13 | ||
PLAT | NM_001319189.2 | c.906A>G | p.Lys302= | synonymous_variant | 9/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLAT | ENST00000220809.9 | c.1173A>G | p.Lys391= | synonymous_variant | 11/14 | 1 | NM_000930.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152270Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251494Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135922
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461846Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18AN XY: 727226
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GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152388Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74520
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at