Variant 3-167465481-T-A 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.671A>T(p.Tyr224Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SERPINI2
NM_006217.6 missense, splice_region

Scores

Splicing: ADA: 0.03194

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

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=0.14468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINI2	NM_006217.6 linkuse as main transcript	c.671A>T	p.Tyr224Phe	missense_variant, splice_region_variant	4/9	ENST00000264677.9
SERPINI2	NM_001012303.3 linkuse as main transcript	c.671A>T	p.Tyr224Phe	missense_variant, splice_region_variant	5/10
SERPINI2	NM_001394327.1 linkuse as main transcript	c.671A>T	p.Tyr224Phe	missense_variant, splice_region_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SERPINI2	ENST00000264677.9 linkuse as main transcript	c.671A>T	p.Tyr224Phe	missense_variant, splice_region_variant	4/9	1	NM_006217.6	P1
SERPINI2	ENST00000461846.5 linkuse as main transcript	c.671A>T	p.Tyr224Phe	missense_variant, splice_region_variant	4/9	1		P1
SERPINI2	ENST00000471111.5 linkuse as main transcript	c.671A>T	p.Tyr224Phe	missense_variant, splice_region_variant	3/8	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

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

Jan 10, 2022

The c.671A>T (p.Y224F) alteration is located in exon 4 (coding exon 3) of the SERPINI2 gene. This alteration results from a A to T substitution at nucleotide position 671, causing the tyrosine (Y) at amino acid position 224 to be replaced by a phenylalanine (F). 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

0.13

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.082

T;T;T;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.68

T;T;.;.;.

M_CAP

Benign

0.027

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.4

L;.;L;L;L

MutationTaster

Benign

0.86

N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

0.75

N;.;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.14

T;.;T;T;T

Sift4G

Benign

0.57

T;T;T;T;T

Polyphen

0.012

B;.;B;B;B

Vest4

0.29

MutPred

0.66

Gain of methylation at K223 (P = 0.0296);.;Gain of methylation at K223 (P = 0.0296);Gain of methylation at K223 (P = 0.0296);Gain of methylation at K223 (P = 0.0296);

MVP

0.47

MPC

0.16

ClinPred

0.15

GERP RS

3.2

Varity_R

0.12

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.032

dbscSNV1_RF

Benign

0.32

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.27

Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over