Variant 18-63933150-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005024.3(SERPINB10):c.736C>T(p.Arg246Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,612,928 control chromosomes in the GnomAD database, including 80,816 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.41 ( 15789 hom., cov: 32)

Exomes 𝑓: 0.29 ( 65027 hom. )

Consequence

SERPINB10
NM_005024.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0430

Variant links:

Genes affected

SERPINB10 (HGNC:8942): (serpin family B member 10) This gene is a member of the serpin peptidase inhibitor, clade B family and is found in a cluster of other similar genes on chromosome 18. The protein encoded by this gene appears to help control the regulation of protease functions during hematopoiesis. Variations in this gene may increase the risk of prostate cancer. [provided by RefSeq, Dec 2015]

SERPINB10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3115061E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SERPINB10	NM_005024.3 linkuse as main transcript	c.736C>T	p.Arg246Cys	missense_variant	7/8	ENST00000238508.8
SERPINB10	XM_011526027.2 linkuse as main transcript	c.736C>T	p.Arg246Cys	missense_variant	8/9
SERPINB10	XM_017025793.2 linkuse as main transcript	c.652C>T	p.Arg218Cys	missense_variant	7/8
SERPINB10	XM_011526028.1 linkuse as main transcript	c.349C>T	p.Arg117Cys	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINB10	ENST00000238508.8 linkuse as main transcript	c.736C>T	p.Arg246Cys	missense_variant	7/8	1	NM_005024.3	P1

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62546

AN:

151860

Hom.:

15746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.708

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.394

GnomAD3 exomes

AF:

0.337

AC:

84627

AN:

251276

Hom.:

16379

AF XY:

0.322

AC XY:

43701

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.717

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.189

Gnomad EAS exome

AF:

0.435

Gnomad SAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.287

AC:

419302

AN:

1460950

Hom.:

65027

Cov.:

AF XY:

0.285

AC XY:

207235

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.724

Gnomad4 AMR exome

AF:

0.449

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.412

AC:

62648

AN:

151978

Hom.:

15789

Cov.:

AF XY:

0.412

AC XY:

30569

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.708

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.439

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.287

Hom.:

17748

Bravo

AF:

0.436

TwinsUK

AF:

0.249

AC:

923

ALSPAC

AF:

0.254

AC:

979

ESP6500AA

AF:

0.695

AC:

3064

ESP6500EA

AF:

0.259

AC:

2224

ExAC

AF:

0.336

AC:

40772

Asia WGS

AF:

0.410

AC:

1425

AN:

3478

EpiCase

AF:

0.270

EpiControl

AF:

0.267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.11

MetaRNN

Benign

0.0000013

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

PROVEAN

Uncertain

-3.6

D;.

REVEL

Benign

0.19

Sift

Benign

0.066

T;.

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.068

B;B

Vest4

0.057

MPC

0.021

ClinPred

0.026

GERP RS

0.68

Varity_R

0.14

gMVP

0.49

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over