Genetic Variant SERPINB3:p.Glu362Lys (chr18-63655746-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006919.3(SERPINB3):c.1084G>A(p.Glu362Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,613,880 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 52 hom. )

Consequence

SERPINB3
NM_006919.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.75

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007921547).

BP6

Variant 18-63655746-C-T is Benign according to our data. Variant chr18-63655746-C-T is described in ClinVar as Benign. ClinVar VariationId is 774727.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006919.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINB3	NM_006919.3	MANE Select	c.1084G>A	p.Glu362Lys	missense	Exon 8 of 8	NP_008850.1	P29508-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINB3	ENST00000283752.10	TSL:1 MANE Select	c.1084G>A	p.Glu362Lys	missense	Exon 8 of 8	ENSP00000283752.5	P29508-1
SERPINB3	ENST00000332821.8	TSL:1	c.928G>A	p.Glu310Lys	missense	Exon 7 of 7	ENSP00000329498.8	P29508-2
SERPINB3	ENST00000864639.1		c.1084G>A	p.Glu362Lys	missense	Exon 8 of 8	ENSP00000534698.1

Frequencies

GnomAD3 genomes

AF:

0.00459

AC:

698

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00400

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00782

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00586

AC:

1471

AN:

251080

AF XY:

0.00611

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00310

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00383

Gnomad NFE exome

AF:

0.00910

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00718

AC:

10500

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00713

AC XY:

5184

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

33470

American (AMR)

AF:

0.00302

AC:

135

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00623

AC:

537

AN:

86254

European-Finnish (FIN)

AF:

0.00432

AC:

231

AN:

53420

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00825

AC:

9172

AN:

1111924

Other (OTH)

AF:

0.00598

AC:

361

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

631

1261

1892

2522

3153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.00459

AC:

698

AN:

152128

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

327

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00109

AC:

AN:

41430

American (AMR)

AF:

0.00399

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00664

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00782

AC:

532

AN:

68020

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

101

134

168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00627

Hom.:

Bravo

AF:

0.00462

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.00657

AC:

798

Asia WGS

AF:

0.00202

AC:

AN:

3476

EpiCase

AF:

0.00693

EpiControl

AF:

0.00694

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.11

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.10

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.19

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.98

PhyloP100

-1.8

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

REVEL

Benign

0.28

Sift

Benign

0.56

Sift4G

Benign

0.32

Polyphen

0.73

Vest4

0.11

MVP

0.65

MPC

0.029

ClinPred

0.0076

GERP RS

-3.3

Varity_R

0.17

gMVP

0.27

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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