Genetic Variant SERPINB13:p.Thr63Met (chr18-63589678-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001348267.2(SERPINB13):c.-214C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,613,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

SERPINB13
NM_001348267.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.159

Variant links:

Genes affected

SERPINB13 (HGNC:8944): (serpin family B member 13) The protein encoded by this gene is a member of the serpin family of serine protease inhibitors. The encoded protein inhibits the activity of cathepsin K and is itself transcriptionally repressed by RUNX1. This gene is downregulated in many types of cancer. [provided by RefSeq, Jan 2017]

SERPINB13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009098709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINB13	NM_012397.4 link	c.188C>T	p.Thr63Met	missense_variant	Exon 3 of 8	ENST00000344731.10	NP_036529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB13	ENST00000344731.10 link	c.188C>T	p.Thr63Met	missense_variant	Exon 3 of 8	1	NM_012397.4	ENSP00000341584.6		Q9UIV8-1

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000509

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000243

AC:

AN:

250922

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000246

AC:

359

AN:

1461360

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

156

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000229

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000277

AC:

AN:

151868

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.000507

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000395

Hom.:

Bravo

AF:

0.000359

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 10, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.188C>T (p.T63M) alteration is located in exon 3 (coding exon 2) of the SERPINB13 gene. This alteration results from a C to T substitution at nucleotide position 188, causing the threonine (T) at amino acid position 63 to be replaced by a methionine (M). 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

0.086

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.4

DANN

Benign

0.86

DEOGEN2

Benign

0.27

T;.;T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.53

T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0091

T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.4

.;.;L;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.0

D;D;D;N

REVEL

Benign

0.17

Sift

Uncertain

0.027

D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

0.036

.;.;B;.

Vest4

0.20, 0.23

MVP

0.53

MPC

0.032

ClinPred

0.042

GERP RS

-0.97

Varity_R

0.052

gMVP

0.18

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