3-167467172-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006217.6(SERPINI2):​c.361G>A​(p.Glu121Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,288 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SERPINI2
NM_006217.6 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.39
Variant links:
Genes affected
SERPINI2 (HGNC:8945): (serpin family I member 2) The gene encodes a member of a family of proteins that acts as inhibitors of serine proteases. These proteins function in the regulation of a variety of physiological processes, including coagulation, fibrinolysis, development, malignancy, and inflammation. Expression of the encoded protein may be downregulated during pancreatic carcinogenesis. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Jan 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERPINI2NM_006217.6 linkc.361G>A p.Glu121Lys missense_variant Exon 3 of 9 ENST00000264677.9 NP_006208.1 O75830B4DDY9
SERPINI2NM_001012303.3 linkc.361G>A p.Glu121Lys missense_variant Exon 4 of 10 NP_001012303.2 O75830B4DDY9
SERPINI2NM_001394327.1 linkc.361G>A p.Glu121Lys missense_variant Exon 4 of 10 NP_001381256.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SERPINI2ENST00000264677.9 linkc.361G>A p.Glu121Lys missense_variant Exon 3 of 9 1 NM_006217.6 ENSP00000264677.4 O75830

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
251086
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135712
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461132
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
726878
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000990
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.361G>A (p.E121K) alteration is located in exon 3 (coding exon 2) of the SERPINI2 gene. This alteration results from a G to A substitution at nucleotide position 361, causing the glutamic acid (E) at amino acid position 121 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
0.0072
T
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.14
T;T;T;T;T;.;T
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.87
D;D;.;.;.;D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.62
D;D;D;D;D;D;D
MetaSVM
Uncertain
0.26
D
MutationAssessor
Benign
1.7
L;.;L;L;L;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.3
N;.;N;N;N;N;N
REVEL
Uncertain
0.36
Sift
Uncertain
0.013
D;.;D;D;D;D;D
Sift4G
Benign
0.25
T;T;T;T;T;T;.
Polyphen
1.0
D;.;D;D;D;.;.
Vest4
0.53
MutPred
0.52
Gain of methylation at E121 (P = 0.0354);.;Gain of methylation at E121 (P = 0.0354);Gain of methylation at E121 (P = 0.0354);Gain of methylation at E121 (P = 0.0354);Gain of methylation at E121 (P = 0.0354);.;
MVP
0.87
MPC
0.72
ClinPred
0.89
D
GERP RS
5.5
Varity_R
0.55
gMVP
0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs760780976; hg19: chr3-167184960; API