18-63935144-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005024.3(SERPINB10):​c.1096C>T​(p.Pro366Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SERPINB10
NM_005024.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2196314).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SERPINB10NM_005024.3 linkuse as main transcriptc.1096C>T p.Pro366Ser missense_variant 8/8 ENST00000238508.8 NP_005015.1 P48595B2RC45
SERPINB10XM_011526027.2 linkuse as main transcriptc.1096C>T p.Pro366Ser missense_variant 9/9 XP_011524329.1 P48595
SERPINB10XM_017025793.2 linkuse as main transcriptc.1012C>T p.Pro338Ser missense_variant 8/8 XP_016881282.1
SERPINB10XM_011526028.1 linkuse as main transcriptc.709C>T p.Pro237Ser missense_variant 6/6 XP_011524330.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SERPINB10ENST00000238508.8 linkuse as main transcriptc.1096C>T p.Pro366Ser missense_variant 8/81 NM_005024.3 ENSP00000238508.3 P48595

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250872
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461184
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
726920
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
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:
0.00000630
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsJul 25, 2024The c.1096C>T (p.P366S) alteration is located in exon 7 (coding exon 7) of the SERPINB10 gene. This alteration results from a C to T substitution at nucleotide position 1096, causing the proline (P) at amino acid position 366 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
0.15
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
20
DANN
Benign
0.94
DEOGEN2
Benign
0.050
T;T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.58
.;T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-0.45
T
MutationAssessor
Benign
1.5
L;L
PROVEAN
Benign
-2.1
N;.
REVEL
Benign
0.23
Sift
Benign
0.41
T;.
Sift4G
Benign
0.40
T;T
Polyphen
0.96
D;D
Vest4
0.20
MutPred
0.28
Gain of phosphorylation at P366 (P = 0.0707);Gain of phosphorylation at P366 (P = 0.0707);
MVP
0.74
MPC
0.10
ClinPred
0.34
T
GERP RS
4.6
Varity_R
0.16
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs764741566; hg19: chr18-61602378; API