Variant 18-63918026-T-C 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.296T>C(p.Ile99Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,611,484 control chromosomes in the GnomAD database, including 33,831 homozygotes. In-silico tool predicts 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 0.24 ( 4503 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29328 hom. )

Consequence

SERPINB10
NM_005024.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46

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=0.0016202629).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB10	NM_005024.3 linkuse as main transcript	c.296T>C	p.Ile99Thr	missense_variant	4/8	ENST00000238508.8	NP_005015.1	P48595B2RC45
SERPINB10	XM_011526027.2 linkuse as main transcript	c.296T>C	p.Ile99Thr	missense_variant	5/9		XP_011524329.1	P48595
SERPINB10	XM_017025793.2 linkuse as main transcript	c.296T>C	p.Ile99Thr	missense_variant	4/8		XP_016881282.1
SERPINB10	XM_011526028.1 linkuse as main transcript	c.-241T>C		5_prime_UTR_variant	1/6		XP_011524330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB10	ENST00000238508.8 linkuse as main transcript	c.296T>C	p.Ile99Thr	missense_variant	4/8	1	NM_005024.3	ENSP00000238508.3		P48595

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35833

AN:

151808

Hom.:

4494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.223

AC:

55782

AN:

250570

Hom.:

6850

AF XY:

0.215

AC XY:

29101

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.219

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.196

AC:

286712

AN:

1459558

Hom.:

29328

Cov.:

AF XY:

0.196

AC XY:

142047

AN XY:

726150

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.189

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.236

AC:

35879

AN:

151926

Hom.:

4503

Cov.:

AF XY:

0.238

AC XY:

17708

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.219

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.194

Hom.:

5851

Bravo

AF:

0.250

TwinsUK

AF:

0.169

AC:

627

ALSPAC

AF:

0.183

AC:

706

ESP6500AA

AF:

0.313

AC:

1379

ESP6500EA

AF:

0.187

AC:

1609

ExAC

AF:

0.216

AC:

26265

Asia WGS

AF:

0.218

AC:

757

AN:

3478

EpiCase

AF:

0.199

EpiControl

AF:

0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.59

.;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.7

M;M

PROVEAN

Uncertain

-3.9

D;.

REVEL

Uncertain

0.39

Sift

Uncertain

0.0090

D;.

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.13

MPC

0.13

ClinPred

0.013

GERP RS

5.8

Varity_R

0.45

gMVP

0.34

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