18-63897119-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002575.3(SERPINB2):​c.317C>T​(p.Ser106Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000021 ( 0 hom. )

Consequence

SERPINB2
NM_002575.3 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.271
Variant links:
Genes affected
SERPINB2 (HGNC:8584): (serpin family B member 2) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in extracellular space. [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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2847442).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERPINB2NM_002575.3 linkc.317C>T p.Ser106Phe missense_variant Exon 4 of 8 ENST00000299502.9 NP_002566.1 P05120
SERPINB2NM_001143818.2 linkc.317C>T p.Ser106Phe missense_variant Exon 5 of 9 NP_001137290.1 P05120
SERPINB2XM_024451192.2 linkc.317C>T p.Ser106Phe missense_variant Exon 4 of 8 XP_024306960.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SERPINB2ENST00000299502.9 linkc.317C>T p.Ser106Phe missense_variant Exon 4 of 8 1 NM_002575.3 ENSP00000299502.4 P05120

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250746
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135520
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
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:
0.00000205
AC:
3
AN:
1460856
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726720
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.029
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.098
T;T;T;T;T
Eigen
Benign
-0.083
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.71
T;.;T;T;T
M_CAP
Benign
0.055
D
MetaRNN
Benign
0.28
T;T;T;T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
1.8
.;L;L;.;.
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.1
N;D;D;D;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.019
D;D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D;D
Polyphen
0.88
.;P;P;.;.
Vest4
0.28, 0.28
MutPred
0.59
Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);Loss of disorder (P = 0.0051);
MVP
0.81
MPC
0.060
ClinPred
0.64
D
GERP RS
3.0
Varity_R
0.23
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs1026386750; hg19: chr18-61564353; API