Variant 3-167465344-C-T 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.728G>A(p.Gly243Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,611,910 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: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

SERPINI2
NM_006217.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09730789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINI2	NM_006217.6 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	5/9	ENST00000264677.9
SERPINI2	NM_001012303.3 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	6/10
SERPINI2	NM_001394327.1 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINI2	ENST00000264677.9 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	5/9	1	NM_006217.6	P1
SERPINI2	ENST00000461846.5 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	5/9	1		P1
SERPINI2	ENST00000471111.5 linkuse as main transcript	c.728G>A	p.Gly243Asp	missense_variant	4/8	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000602

AC:

AN:

249154

Hom.:

AF XY:

0.0000669

AC XY:

AN XY:

134566

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000585

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:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000569

AC:

AN:

1459802

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.0000684

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000989

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Aug 17, 2021

The c.728G>A (p.G243D) alteration is located in exon 5 (coding exon 4) of the SERPINI2 gene. This alteration results from a G to A substitution at nucleotide position 728, causing the glycine (G) at amino acid position 243 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Uncertain

0.45

T;T;T;T;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.44

T;T;.;.;.

M_CAP

Benign

0.038

MetaRNN

Benign

0.097

T;T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.9

L;.;L;L;L

MutationTaster

Benign

0.82

D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-4.8

D;.;D;D;D

REVEL

Benign

0.18

Sift

Benign

0.036

D;.;D;D;D

Sift4G

Uncertain

0.057

T;T;T;T;T

Polyphen

0.17

B;.;B;B;B

Vest4

0.23

MVP

0.44

MPC

0.25

ClinPred

0.071

GERP RS

2.8

Varity_R

0.38

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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