Variant chr3-167467247-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006217.6(SERPINI2):c.286A>G(p.Ile96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SERPINI2
NM_006217.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24109781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINI2	NM_006217.6 linkuse as main transcript	c.286A>G	p.Ile96Val	missense_variant	3/9	ENST00000264677.9
SERPINI2	NM_001012303.3 linkuse as main transcript	c.286A>G	p.Ile96Val	missense_variant	4/10
SERPINI2	NM_001394327.1 linkuse as main transcript	c.286A>G	p.Ile96Val	missense_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINI2	ENST00000264677.9 linkuse as main transcript	c.286A>G	p.Ile96Val	missense_variant	3/9	1	NM_006217.6	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249610

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460412

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726508

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.286A>G (p.I96V) alteration is located in exon 3 (coding exon 2) of the SERPINI2 gene. This alteration results from a A to G substitution at nucleotide position 286, causing the isoleucine (I) at amino acid position 96 to be replaced by a valine (V). 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

0.081

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;T;T;T;.

Eigen

Benign

0.027

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.71

T;T;.;.;.;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.24

T;T;T;T;T;T

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

1.5

L;.;L;L;L;.

MutationTaster

Benign

0.92

D;D;D;D

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.71

N;.;N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.56

T;.;T;T;T;T

Sift4G

Benign

0.084

T;T;T;T;T;T

Polyphen

0.35

B;.;B;B;B;.

Vest4

0.12

MutPred

0.64

Gain of catalytic residue at I96 (P = 0.0645);.;Gain of catalytic residue at I96 (P = 0.0645);Gain of catalytic residue at I96 (P = 0.0645);Gain of catalytic residue at I96 (P = 0.0645);Gain of catalytic residue at I96 (P = 0.0645);

MVP

0.66

MPC

0.41

ClinPred

0.16

GERP RS

5.4

Varity_R

0.22

gMVP

0.091

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.

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