Variant 18-63915633-A-G 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.123A>G(p.Ile41Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,611,480 control chromosomes in the GnomAD database, including 64,404 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.39 ( 15935 hom., cov: 32)

Exomes 𝑓: 0.24 ( 48469 hom. )

Consequence

SERPINB10
NM_005024.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17

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:

ENSG00000289724 (HGNC:):

ENSG00000289724 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2298226E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 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.123A>G	p.Ile41Met	missense_variant	2/8	ENST00000238508.8	NP_005015.1	P48595B2RC45
SERPINB10	XM_011526027.2 linkuse as main transcript	c.123A>G	p.Ile41Met	missense_variant	3/9		XP_011524329.1	P48595
SERPINB10	XM_017025793.2 linkuse as main transcript	c.123A>G	p.Ile41Met	missense_variant	2/8		XP_016881282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SERPINB10	ENST00000238508.8 linkuse as main transcript	c.123A>G	p.Ile41Met	missense_variant	2/8	1	NM_005024.3	ENSP00000238508.3	P48595
ENSG00000289724	ENST00000397996.6 linkuse as main transcript	c.759A>G	p.Ile253Met	missense_variant	7/8	5		ENSP00000381082.2	H7BYS2
ENSG00000289724	ENST00000418725.1 linkuse as main transcript	c.678A>G	p.Ile226Met	missense_variant	6/7	5		ENSP00000392381.1	H7C004

Frequencies

GnomAD3 genomes

AF:

0.389

AC:

59032

AN:

151706

Hom.:

15875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.757

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.374

GnomAD3 exomes

AF:

0.301

AC:

75426

AN:

250218

Hom.:

14535

AF XY:

0.284

AC XY:

38448

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.767

Gnomad AMR exome

AF:

0.445

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.435

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.236

AC:

345070

AN:

1459656

Hom.:

48469

Cov.:

AF XY:

0.235

AC XY:

170732

AN XY:

726168

show subpopulations

Gnomad4 AFR exome

AF:

0.775

Gnomad4 AMR exome

AF:

0.435

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.270

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.390

AC:

59155

AN:

151824

Hom.:

15935

Cov.:

AF XY:

0.389

AC XY:

28864

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.757

Gnomad4 AMR

AF:

0.406

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.285

Gnomad4 FIN

AF:

0.226

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.379

Alfa

AF:

0.242

Hom.:

13244

Bravo

AF:

0.421

TwinsUK

AF:

0.186

AC:

688

ALSPAC

AF:

0.198

AC:

762

ESP6500AA

AF:

0.741

AC:

3266

ESP6500EA

AF:

0.204

AC:

1752

ExAC

AF:

0.301

AC:

36496

Asia WGS

AF:

0.406

AC:

1410

AN:

3478

EpiCase

AF:

0.218

EpiControl

AF:

0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.15

DEOGEN2

Benign

0.029

T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.085

.;T

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.8

N;N

PROVEAN

Benign

3.0

N;.

REVEL

Uncertain

0.30

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.044

MPC

0.018

ClinPred

0.0063

GERP RS

5.8

Varity_R

0.14

gMVP

0.17

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