Genetic Variant SERPINI2:p.Asp316Asn (chr3-167452954-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006217.6(SERPINI2):c.946G>A(p.Asp316Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,598,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SERPINI2
NM_006217.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18774474).

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.946G>A	p.Asp316Asn	missense	Exon 6 of 9	NP_006208.1	O75830
SERPINI2	NM_001012303.3		c.946G>A	p.Asp316Asn	missense	Exon 7 of 10	NP_001012303.2	O75830
SERPINI2	NM_001394327.1		c.946G>A	p.Asp316Asn	missense	Exon 7 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.946G>A	p.Asp316Asn	missense	Exon 6 of 9	ENSP00000264677.4	O75830
SERPINI2	ENST00000461846.5	TSL:1	c.946G>A	p.Asp316Asn	missense	Exon 6 of 9	ENSP00000417692.1	O75830
SERPINI2	ENST00000471111.5	TSL:1	c.946G>A	p.Asp316Asn	missense	Exon 5 of 8	ENSP00000419407.1	O75830

Frequencies

GnomAD3 genomes

AF:

0.0000528

AC:

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.0000247

AC:

AN:

243098

AF XY:

0.0000381

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1446780

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

719762

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32720

American (AMR)

AF:

0.0000231

AC:

AN:

43218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25744

East Asian (EAS)

AF:

0.0000507

AC:

AN:

39432

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.00000997

AC:

AN:

1103682

Other (OTH)

AF:

0.0000669

AC:

AN:

59774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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

AF:

0.0000527

AC:

AN:

151732

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41368

American (AMR)

AF:

0.000131

AC:

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000581

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67942

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

Eigen

Benign

0.12

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.75

M_CAP

Benign

0.051

MetaRNN

Benign

0.19

MetaSVM

Uncertain

0.051

MutationAssessor

Benign

1.5

PhyloP100

3.0

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.42

Sift

Benign

0.30

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.29

MVP

0.65

MPC

0.30

ClinPred

0.34

GERP RS

3.7

Varity_R

0.31

gMVP

0.46

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over