3-167449372-G-A

Position:

chr3-167449372-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006217.6(SERPINI2):c.995C>T(p.Thr332Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000745 in 1,611,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

SERPINI2
NM_006217.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.727

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016834944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINI2	NM_006217.6 linkuse as main transcript	c.995C>T	p.Thr332Met	missense_variant	7/9	ENST00000264677.9	NP_006208.1	O75830B4DDY9
SERPINI2	NM_001012303.3 linkuse as main transcript	c.995C>T	p.Thr332Met	missense_variant	8/10		NP_001012303.2	O75830B4DDY9
SERPINI2	NM_001394327.1 linkuse as main transcript	c.995C>T	p.Thr332Met	missense_variant	8/10		NP_001381256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SERPINI2	ENST00000264677.9 linkuse as main transcript	c.995C>T	p.Thr332Met	missense_variant	7/9	1	NM_006217.6	ENSP00000264677.4	O75830
SERPINI2	ENST00000461846.5 linkuse as main transcript	c.995C>T	p.Thr332Met	missense_variant	7/9	1		ENSP00000417692.1	O75830
SERPINI2	ENST00000471111.5 linkuse as main transcript	c.995C>T	p.Thr332Met	missense_variant	6/8	1		ENSP00000419407.1	O75830

Frequencies

GnomAD3 genomes

AF:

0.0000792

AC:

AN:

151572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000329

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000964

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000151

AC:

AN:

250882

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000740

AC:

108

AN:

1460040

Hom.:

Cov.:

AF XY:

0.0000702

AC XY:

AN XY:

726488

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000792

AC:

AN:

151572

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

73948

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.000329

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000964

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000547

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 07, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.27

DEOGEN2

Benign

0.085

T;T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.24

T;T;.;.;.

M_CAP

Benign

0.027

MetaRNN

Benign

0.017

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.4

N;.;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

1.7

N;.;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.62

T;.;T;T;T

Sift4G

Benign

0.37

T;T;T;T;T

Polyphen

0.0030

B;.;B;B;B

Vest4

0.067

MutPred

0.46

Gain of catalytic residue at V328 (P = 0.0203);.;Gain of catalytic residue at V328 (P = 0.0203);Gain of catalytic residue at V328 (P = 0.0203);Gain of catalytic residue at V328 (P = 0.0203);

MVP

0.15

MPC

0.17

ClinPred

0.028

GERP RS

2.0

Varity_R

0.025

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over