Variant chr18-63918068-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005024.3(SERPINB10):c.338C>T(p.Ala113Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000782 in 1,612,120 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 2 hom. )

Consequence

SERPINB10
NM_005024.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.841

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012789637).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SERPINB10	NM_005024.3 linkuse as main transcript	c.338C>T	p.Ala113Val	missense_variant	4/8	ENST00000238508.8	NP_005015.1
SERPINB10	XM_011526027.2 linkuse as main transcript	c.338C>T	p.Ala113Val	missense_variant	5/9		XP_011524329.1
SERPINB10	XM_017025793.2 linkuse as main transcript	c.338C>T	p.Ala113Val	missense_variant	4/8		XP_016881282.1
SERPINB10	XM_011526028.1 linkuse as main transcript	c.-199C>T		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.338C>T	p.Ala113Val	missense_variant	4/8	1	NM_005024.3	ENSP00000238508	P1

Frequencies

GnomAD3 genomes

AF:

0.000750

AC:

114

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000868

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000874

AC:

219

AN:

250618

Hom.:

AF XY:

0.000886

AC XY:

120

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000581

Gnomad ASJ exome

AF:

0.00626

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.000786

AC:

1147

AN:

1460088

Hom.:

Cov.:

AF XY:

0.000781

AC XY:

567

AN XY:

726378

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000875

Gnomad4 ASJ exome

AF:

0.00625

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000784

Gnomad4 OTH exome

AF:

0.000813

GnomAD4 genome

AF:

0.000750

AC:

114

AN:

152032

Hom.:

Cov.:

AF XY:

0.000848

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.000868

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000733

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000667

AC:

EpiCase

AF:

0.00153

EpiControl

AF:

0.00178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.338C>T (p.A113V) alteration is located in exon 3 (coding exon 3) of the SERPINB10 gene. This alteration results from a C to T substitution at nucleotide position 338, causing the alanine (A) at amino acid position 113 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.033

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.075

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.27

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.92

P;P

Vest4

0.15

MVP

0.73

MPC

0.045

ClinPred

0.017

GERP RS

3.1

Varity_R

0.11

gMVP

0.39

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