rs121909051
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_001122752.2(SERPINI1):c.145T>C(p.Ser49Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. S49S) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
SERPINI1
NM_001122752.2 missense
NM_001122752.2 missense
Scores
11
6
1
Clinical Significance
Conservation
PhyloP100: 7.15
Genes affected
SERPINI1 (HGNC:8943): (serpin family I member 1) This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The protein is primarily secreted by axons in the brain, and preferentially reacts with and inhibits tissue-type plasminogen activator. It is thought to play a role in the regulation of axonal growth and the development of synaptic plasticity. Mutations in this gene result in familial encephalopathy with neuroserpin inclusion bodies (FENIB), which is a dominantly inherited form of familial encephalopathy and epilepsy characterized by the accumulation of mutant neuroserpin polymers. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.989
PP5
?
Variant 3-167789273-T-C is Pathogenic according to our data. Variant chr3-167789273-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 7086.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINI1 | NM_001122752.2 | c.145T>C | p.Ser49Pro | missense_variant | 2/9 | ENST00000446050.7 | |
SERPINI1 | NM_005025.5 | c.145T>C | p.Ser49Pro | missense_variant | 2/9 | ||
SERPINI1 | XM_017006618.3 | c.145T>C | p.Ser49Pro | missense_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINI1 | ENST00000446050.7 | c.145T>C | p.Ser49Pro | missense_variant | 2/9 | 1 | NM_001122752.2 | P1 | |
SERPINI1 | ENST00000295777.9 | c.145T>C | p.Ser49Pro | missense_variant | 2/9 | 1 | P1 | ||
SERPINI1 | ENST00000472747.2 | c.145T>C | p.Ser49Pro | missense_variant | 2/5 | 3 | |||
SERPINI1 | ENST00000472941.5 | c.145T>C | p.Ser49Pro | missense_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
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
Familial encephalopathy with neuroserpin inclusion bodies Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 02, 2004 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;D;D;.
Vest4
0.90
MutPred
Gain of glycosylation at P50 (P = 0.153);Gain of glycosylation at P50 (P = 0.153);Gain of glycosylation at P50 (P = 0.153);Gain of glycosylation at P50 (P = 0.153);
MVP
MPC
0.54
ClinPred
D
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