Genetic Variant NM_006919.3:c.604C>T (chr18-63657278-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006919.3(SERPINB3):c.604C>T(p.Pro202Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,562,818 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

SERPINB3
NM_006919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.363

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.062802196).

BS2

High Homozygotes in GnomAdExome4 at 5 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.604C>T	p.Pro202Ser	missense	Exon 6 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.604C>T	p.Pro202Ser	missense	Exon 6 of 8	ENSP00000283752.5	P29508-1
SERPINB3	ENST00000332821.8	TSL:1	c.604C>T	p.Pro202Ser	missense	Exon 6 of 7	ENSP00000329498.8	P29508-2
SERPINB3	ENST00000864639.1		c.604C>T	p.Pro202Ser	missense	Exon 6 of 8	ENSP00000534698.1

Frequencies

GnomAD3 genomes

AF:

0.000612

AC:

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000919

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:

0.00104

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000422

AC:

102

AN:

241506

AF XY:

0.000413

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.000247

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000785

Gnomad OTH exome

AF:

0.000518

GnomAD4 exome

AF:

0.00114

AC:

1605

AN:

1410882

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

752

AN XY:

702546

show subpopulations

African (AFR)

AF:

0.000187

AC:

AN:

32094

American (AMR)

AF:

0.000331

AC:

AN:

42352

Ashkenazi Jewish (ASJ)

AF:

0.0000395

AC:

AN:

25306

East Asian (EAS)

AF:

0.00

AC:

AN:

39120

South Asian (SAS)

AF:

0.00

AC:

AN:

79272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5594

European-Non Finnish (NFE)

AF:

0.00139

AC:

1493

AN:

1076424

Other (OTH)

AF:

0.00156

AC:

AN:

58360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

130

194

259

324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.000612

AC:

AN:

151936

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41376

American (AMR)

AF:

0.000919

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000716

Hom.:

Bravo

AF:

0.000631

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000321

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

0.20

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.065

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.18

M_CAP

Benign

0.072

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.63

MutationAssessor

Benign

-0.12

PhyloP100

-0.36

PrimateAI

Benign

0.26

PROVEAN

Benign

0.23

REVEL

Benign

0.26

Sift

Uncertain

0.013

Sift4G

Uncertain

0.0040

Polyphen

0.54

Vest4

0.13

MVP

0.78

MPC

0.024

ClinPred

0.019

GERP RS

1.8

Varity_R

0.19

gMVP

0.69

Mutation Taster

=84/16

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