3-167794703-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001122752.2(SERPINI1):​c.760A>T​(p.Met254Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SERPINI1
NM_001122752.2 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.09
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.36395308).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERPINI1NM_001122752.2 linkc.760A>T p.Met254Leu missense_variant Exon 5 of 9 ENST00000446050.7 NP_001116224.1 Q99574A0A0S2Z455
SERPINI1NM_005025.5 linkc.760A>T p.Met254Leu missense_variant Exon 5 of 9 NP_005016.1 Q99574A0A0S2Z455
SERPINI1XM_017006618.3 linkc.760A>T p.Met254Leu missense_variant Exon 5 of 9 XP_016862107.1 Q99574A0A0S2Z455

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SERPINI1ENST00000446050.7 linkc.760A>T p.Met254Leu missense_variant Exon 5 of 9 1 NM_001122752.2 ENSP00000397373.2 Q99574
SERPINI1ENST00000295777.9 linkc.760A>T p.Met254Leu missense_variant Exon 5 of 9 1 ENSP00000295777.5 Q99574
SERPINI1ENST00000472747.2 linkc.*24A>T downstream_gene_variant 3 ENSP00000420561.2 C9JDY5
ENSG00000287319ENST00000661269.1 linkn.*244T>A downstream_gene_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461488
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727050
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
19
DANN
Benign
0.81
DEOGEN2
Benign
0.12
T;T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.067
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.81
.;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.36
T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
0.23
N;N
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
0.64
N;N
REVEL
Uncertain
0.41
Sift
Benign
0.98
T;T
Sift4G
Benign
0.78
T;T
Polyphen
0.0
B;B
Vest4
0.60
MutPred
0.53
Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);
MVP
0.65
MPC
0.085
ClinPred
0.78
D
GERP RS
5.7
Varity_R
0.88
gMVP
0.37

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: chr3-167512491; API