chr18-63484472-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002639.5(SERPINB5):āc.44T>Cā(p.Leu15Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000669 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000092 ( 0 hom., cov: 33)
Exomes š: 0.000064 ( 0 hom. )
Consequence
SERPINB5
NM_002639.5 missense
NM_002639.5 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 5.50
Genes affected
SERPINB5 (HGNC:8949): (serpin family B member 5) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within several processes, including extracellular matrix organization; prostate gland morphogenesis; and regulation of epithelial cell proliferation. Located in cytoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
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 | UniProt |
---|---|---|---|---|---|---|---|
SERPINB5 | NM_002639.5 | c.44T>C | p.Leu15Pro | missense_variant | 2/7 | ENST00000382771.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINB5 | ENST00000382771.9 | c.44T>C | p.Leu15Pro | missense_variant | 2/7 | 1 | NM_002639.5 | P1 | |
SERPINB5 | ENST00000489441.5 | c.44T>C | p.Leu15Pro | missense_variant | 2/5 | 1 | |||
SERPINB5 | ENST00000424602.1 | c.44T>C | p.Leu15Pro | missense_variant | 2/4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152242Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
14
AN:
152242
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000139 AC: 35AN: 250936Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135616
GnomAD3 exomes
AF:
AC:
35
AN:
250936
Hom.:
AF XY:
AC XY:
11
AN XY:
135616
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461544Hom.: 0 Cov.: 31 AF XY: 0.0000605 AC XY: 44AN XY: 727074
GnomAD4 exome
AF:
AC:
94
AN:
1461544
Hom.:
Cov.:
31
AF XY:
AC XY:
44
AN XY:
727074
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74378
GnomAD4 genome
AF:
AC:
14
AN:
152242
Hom.:
Cov.:
33
AF XY:
AC XY:
8
AN XY:
74378
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
12
EpiCase
AF:
EpiControl
AF:
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 | Sep 22, 2022 | The c.44T>C (p.L15P) alteration is located in exon 2 (coding exon 1) of the SERPINB5 gene. This alteration results from a T to C substitution at nucleotide position 44, causing the leucine (L) at amino acid position 15 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Pathogenic
D;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D
REVEL
Pathogenic
Sift
Pathogenic
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at