Variant 18-63915652-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005024.3(SERPINB10):c.142G>A(p.Gly48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SERPINB10
NM_005024.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB10	NM_005024.3 linkuse as main transcript	c.142G>A	p.Gly48Ser	missense_variant	2/8	ENST00000238508.8	NP_005015.1	P48595B2RC45
SERPINB10	XM_011526027.2 linkuse as main transcript	c.142G>A	p.Gly48Ser	missense_variant	3/9		XP_011524329.1	P48595
SERPINB10	XM_017025793.2 linkuse as main transcript	c.142G>A	p.Gly48Ser	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.142G>A	p.Gly48Ser	missense_variant	2/8	1	NM_005024.3	ENSP00000238508.3	P48595
ENSG00000289724	ENST00000397996.6 linkuse as main transcript	c.778G>A	p.Gly260Ser	missense_variant	7/8	5		ENSP00000381082.2	H7BYS2
ENSG00000289724	ENST00000418725.1 linkuse as main transcript	c.697G>A	p.Gly233Ser	missense_variant	6/7	5		ENSP00000392381.1	H7C004

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459598

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 16, 2024

The c.142G>A (p.G48S) alteration is located in exon 1 (coding exon 1) of the SERPINB10 gene. This alteration results from a G to A substitution at nucleotide position 142, causing the glycine (G) at amino acid position 48 to be replaced by a serine (S). 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

0.27

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PROVEAN

Pathogenic

-4.8

D;.

REVEL

Benign

0.25

Sift

Uncertain

0.026

D;.

Sift4G

Uncertain

0.039

D;D

Polyphen

0.099

B;B

Vest4

0.27

MutPred

0.76

Loss of catalytic residue at G48 (P = 0.0475);Loss of catalytic residue at G48 (P = 0.0475);

MVP

0.83

MPC

0.035

ClinPred

0.76

GERP RS

2.0

Varity_R

0.32

gMVP

0.38

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over