Genetic Variant SERPINI2:p.Ala268Pro (chr3-167465270-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006217.6(SERPINI2):c.802G>C(p.Ala268Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A268T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SERPINI2
NM_006217.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.718

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22202864).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006217.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINI2	NM_006217.6	MANE Select	c.802G>C	p.Ala268Pro	missense	Exon 5 of 9	NP_006208.1	O75830
SERPINI2	NM_001012303.3		c.802G>C	p.Ala268Pro	missense	Exon 6 of 10	NP_001012303.2	O75830
SERPINI2	NM_001394327.1		c.802G>C	p.Ala268Pro	missense	Exon 6 of 10	NP_001381256.1	O75830

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINI2	ENST00000264677.9	TSL:1 MANE Select	c.802G>C	p.Ala268Pro	missense	Exon 5 of 9	ENSP00000264677.4	O75830
SERPINI2	ENST00000461846.5	TSL:1	c.802G>C	p.Ala268Pro	missense	Exon 5 of 9	ENSP00000417692.1	O75830
SERPINI2	ENST00000471111.5	TSL:1	c.802G>C	p.Ala268Pro	missense	Exon 4 of 8	ENSP00000419407.1	O75830

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250122

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460530

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111690

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.22

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.71

M_CAP

Benign

0.045

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.74

PhyloP100

0.72

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.1

REVEL

Benign

0.20

Sift

Benign

0.27

Sift4G

Benign

0.17

Polyphen

0.028

Vest4

0.20

MutPred

0.63

Gain of catalytic residue at A268 (P = 0.0263)

MVP

0.80

MPC

0.76

ClinPred

0.21

GERP RS

2.8

Varity_R

0.51

gMVP

0.90

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over