rs121965062
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_000934.4(SERPINF2):c.1231G>A(p.Val411Met) 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 pathogenic outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
SERPINF2
NM_000934.4 missense
NM_000934.4 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: -0.196
Genes affected
SERPINF2 (HGNC:9075): (serpin family F member 2) This gene encodes a member of the serpin family of serine protease inhibitors. The protein is a major inhibitor of plasmin, which degrades fibrin and various other proteins. Consequently, the proper function of this gene has a major role in regulating the blood clotting pathway. Mutations in this gene result in alpha-2-plasmin inhibitor deficiency, which is characterized by severe hemorrhagic diathesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.864
PP5
Variant 17-1754289-G-A is Pathogenic according to our data. Variant chr17-1754289-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 276.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-1754289-G-A is described in UniProt as null. Variant chr17-1754289-G-A is described in UniProt as null.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SERPINF2 | NM_000934.4 | c.1231G>A | p.Val411Met | missense_variant | 10/10 | ENST00000453066.6 | NP_000925.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SERPINF2 | ENST00000453066.6 | c.1231G>A | p.Val411Met | missense_variant | 10/10 | 5 | NM_000934.4 | ENSP00000402286 | P1 | |
SERPINF2 | ENST00000382061.5 | c.1231G>A | p.Val411Met | missense_variant | 10/10 | 1 | ENSP00000371493 | P1 | ||
SERPINF2 | ENST00000324015.7 | c.1231G>A | p.Val411Met | missense_variant | 10/10 | 5 | ENSP00000321853 | P1 | ||
SERPINF2 | ENST00000450523.6 | c.1039G>A | p.Val347Met | missense_variant | 9/9 | 2 | ENSP00000403877 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Alpha-2-plasmin inhibitor deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
D;D;.
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
A;A;A
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
D;.;D
Vest4
MutPred
Gain of disorder (P = 0.0483);.;Gain of disorder (P = 0.0483);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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