Variant 18-63658582-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006919.3(SERPINB3):c.400G>A(p.Val134Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0114 in 1,591,476 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V134A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0097 ( 15 hom., cov: 31)

Exomes 𝑓: 0.012 ( 276 hom. )

Consequence

SERPINB3
NM_006919.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.62

Variant links:

Genes affected

SERPINB3 (HGNC:10569): (serpin family B member 3) Enables cysteine-type endopeptidase inhibitor activity; protease binding activity; and virus receptor activity. Involved in several processes, including autocrine signaling; paracrine signaling; and regulation of cellular protein metabolic process. Located in cytoplasmic vesicle; extracellular exosome; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SERPINB3 links:

SERPINB11 (HGNC:14221): (serpin family B member 11) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in cytoplasm. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SERPINB11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0123381615).

BP6

Variant 18-63658582-C-T is Benign according to our data. Variant chr18-63658582-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648794.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINB3	NM_006919.3 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	5/8	ENST00000283752.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB3	ENST00000283752.10 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	5/8	1	NM_006919.3	P1	P29508-1
SERPINB3	ENST00000332821.8 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	5/7	1			P29508-2
SERPINB11	ENST00000489748.5 linkuse as main transcript	c.-16+2606C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00969

AC:

1465

AN:

151140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.0309

Gnomad AMR

AF:

0.00850

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.00881

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0157

Gnomad OTH

AF:

0.00725

GnomAD3 exomes

AF:

0.00175

AC:

437

AN:

250402

Hom.:

AF XY:

0.00182

AC XY:

246

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.00218

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000981

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.0115

AC:

16619

AN:

1440218

Hom.:

276

Cov.:

AF XY:

0.0113

AC XY:

8104

AN XY:

716956

show subpopulations

Gnomad4 AFR exome

AF:

0.00225

Gnomad4 AMR exome

AF:

0.00580

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00382

Gnomad4 FIN exome

AF:

0.00811

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00969

AC:

1465

AN:

151258

Hom.:

Cov.:

AF XY:

0.00895

AC XY:

662

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.00261

Gnomad4 AMR

AF:

0.00842

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.00881

Gnomad4 NFE

AF:

0.0157

Gnomad4 OTH

AF:

0.00717

Alfa

AF:

0.00643

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

SERPINB3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.048

D;D

Polyphen

0.0010

B;B

Vest4

0.28

MVP

0.41

MPC

0.040

ClinPred

0.028

GERP RS

2.0

Varity_R

0.23

gMVP

0.081

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

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