SERPINE1 p.Ala119Ala

Variant names:

• chr7-101130503-C-C
• ENST00000223095.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr7-101130504--
• chr7-101130506-G-T
• chr7-101130506-G-C
• chr7-101130506-G-A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The ENST00000223095.5(SERPINE1):​c. variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SERPINE1 ENST00000223095.5 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.18
• Publications: 0 publications found

Genes affected

SERPINE1 (HGNC:8583): (serpin family E member 1) This gene encodes a member of the serine proteinase inhibitor (serpin) superfamily. This member is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), and hence is an inhibitor of fibrinolysis. The protein also functions as a component of innate antiviral immunity. Defects in this gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the gene product are associated with thrombophilia. [provided by RefSeq, Aug 2020]

SERPINE1 Gene-Disease associations (from GenCC):

• congenital plasminogen activator inhibitor type 1 deficiency

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.19354838 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000223095.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE1	ENST00000223095.5	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000223095.4	P05121-1
	SERPINE1	ENST00000950060.1		c.		splice_donor intron	N/A	ENSP00000620119.1
	SERPINE1	ENST00000950062.1		c.		splice_donor intron	N/A	ENSP00000620121.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-100773784;