8-42179964-GTC-ATA

Position:

• chr8-42179964-GTC-ATA

Variant summary

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

The NM_000930.5(PLAT):​c.1323_1325delinsTAT​(p.Trp441_Thr442delinsCysMet) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLAT NM_000930.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 7.37

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]

ACMG classification

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/exons	MANE	Protein	UniProt
PLAT	NM_000930.5	c.1323_1325delinsTAT	p.Trp441_Thr442delinsCysMet	missense_variant	12/14	ENST00000220809.9	NP_000921.1
PLAT	NM_001319189.2	c.1056_1058delinsTAT	p.Trp352_Thr353delinsCysMet	missense_variant	10/12		NP_001306118.1
PLAT	NM_033011.4	c.1185_1187delinsTAT	p.Trp395_Thr396delinsCysMet	missense_variant	11/13		NP_127509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAT	ENST00000220809.9	c.1323_1325delinsTAT	p.Trp441_Thr442delinsCysMet	missense_variant	12/14	1	NM_000930.5	ENSP00000220809	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Hereditary angioedema with normal C1Inh Other:1

not provided, no classification provided

literature only

CeMIA

Feb 01, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1587927986; hg19: chr8-42037482;