Variant 3-167471596-G-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.239C>G(p.Thr80Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,106 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SERPINI2
NM_006217.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.105

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:

LOC105374197 (HGNC:):

LOC105374197 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=0.07635465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINI2	NM_006217.6 linkuse as main transcript	c.239C>G	p.Thr80Ser	missense_variant	2/9	ENST00000264677.9
LOC105374197	XR_924683.3 linkuse as main transcript	n.127+475G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINI2	ENST00000264677.9 linkuse as main transcript	c.239C>G	p.Thr80Ser	missense_variant	2/9	1	NM_006217.6	P1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461072

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Mar 16, 2022

The c.239C>G (p.T80S) alteration is located in exon 2 (coding exon 1) of the SERPINI2 gene. This alteration results from a C to G substitution at nucleotide position 239, causing the threonine (T) at amino acid position 80 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.17

DANN

Benign

0.28

DEOGEN2

Benign

0.078

T;T;T;T;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.41

T;T;.;.;.;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.076

T;T;T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.96

L;.;L;L;L;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.050

N;.;N;N;N;N;N

REVEL

Benign

0.096

Sift

Benign

0.75

T;.;T;T;T;T;T

Sift4G

Benign

0.77

T;T;T;T;T;T;.

Polyphen

0.042

B;.;B;B;B;.;.

Vest4

0.064

MutPred

0.41

Gain of disorder (P = 0.0604);.;Gain of disorder (P = 0.0604);Gain of disorder (P = 0.0604);Gain of disorder (P = 0.0604);Gain of disorder (P = 0.0604);Gain of disorder (P = 0.0604);

MVP

0.31

MPC

0.15

ClinPred

0.084

GERP RS

-2.9

Varity_R

0.046

gMVP

0.063

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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