Genetic Variant SERPINI2:p.Gly243Val (chr3-167465344-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_006217.6(SERPINI2):c.728G>T(p.Gly243Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,028 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SERPINI2
NM_006217.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

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]

SERPINI2 links:

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=0.40421456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINI2	NM_006217.6 link	c.728G>T	p.Gly243Val	missense_variant	Exon 5 of 9	ENST00000264677.9	NP_006208.1	O75830B4DDY9
SERPINI2	NM_001012303.3 link	c.728G>T	p.Gly243Val	missense_variant	Exon 6 of 10		NP_001012303.2	O75830B4DDY9
SERPINI2	NM_001394327.1 link	c.728G>T	p.Gly243Val	missense_variant	Exon 6 of 10		NP_001381256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINI2	ENST00000264677.9 link	c.728G>T	p.Gly243Val	missense_variant	Exon 5 of 9	1	NM_006217.6	ENSP00000264677.4	O75830
SERPINI2	ENST00000461846.5 link	c.728G>T	p.Gly243Val	missense_variant	Exon 5 of 9	1		ENSP00000417692.1	O75830
SERPINI2	ENST00000471111.5 link	c.728G>T	p.Gly243Val	missense_variant	Exon 4 of 8	1		ENSP00000419407.1	O75830
SERPINI2	ENST00000466903.1 link	c.*190G>T		downstream_gene_variant		3		ENSP00000417752.1	C9J7N5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249154

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459802

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.65

D;T;D;D;D

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.46

T;T;.;.;.

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.40

T;T;T;T;T

MetaSVM

Uncertain

0.15

MutationAssessor

Pathogenic

3.9

H;.;H;H;H

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-6.5

D;.;D;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

D;.;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D

Polyphen

0.96

D;.;D;D;D

Vest4

0.41

MVP

0.74

MPC

0.67

ClinPred

0.95

GERP RS

2.8

Varity_R

0.82

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over