8-42187447-G-C

Variant names:

• chr8-42187447-G-C
• NM_000930.5:c.490C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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. 13/21 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. R164W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLAT NM_000930.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34313175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAT	NM_000930.5	c.490C>G	p.Arg164Gly	missense_variant	Exon 6 of 14	ENST00000220809.9	NP_000921.1
PLAT	NM_033011.4	c.352C>G	p.Arg118Gly	missense_variant	Exon 5 of 13		NP_127509.1
PLAT	NM_001319189.2	c.364+459C>G		intron_variant	Intron 5 of 11		NP_001306118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAT	ENST00000220809.9	c.490C>G	p.Arg164Gly	missense_variant	Exon 6 of 14	1	NM_000930.5	ENSP00000220809.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;T;.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.85	.;T;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.3	M;M;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.13
Sift	Benign	0.085	T;T;T;D
Sift4G	Benign	0.16	T;T;T;.
Polyphen		0.51	P;P;B;.
Vest4		0.49
MutPred		0.60		Gain of ubiquitination at K159 (P = 0.034);Gain of ubiquitination at K159 (P = 0.034);.;Gain of ubiquitination at K159 (P = 0.034);
MVP		0.68
MPC		0.73
ClinPred		0.95	D
GERP RS		1.9
Varity_R		0.51
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-42044965;