rs193921093
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002974.4(SERPINB4):c.476T>A(p.Ile159Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
SERPINB4
NM_002974.4 missense
NM_002974.4 missense
Scores
9
7
2
Clinical Significance
Conservation
PhyloP100: 6.09
Genes affected
SERPINB4 (HGNC:10570): (serpin family B member 4) The protein encoded by this gene is a member of the serpin family of serine protease inhibitors. The encoded protein is highly expressed in many tumor cells and can inactivate granzyme M, an enzyme that kills tumor cells. This protein, along with serpin B3, can be processed into smaller fragments that aggregate to form an autoantigen in psoriasis, probably by causing chronic inflammation. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.964
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SERPINB4 | NM_002974.4 | c.476T>A | p.Ile159Asn | missense_variant | 6/8 | ENST00000341074.10 | |
SERPINB4 | NM_175041.2 | c.476T>A | p.Ile159Asn | missense_variant | 6/8 | ||
SERPINB4 | XM_011526138.2 | c.476T>A | p.Ile159Asn | missense_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SERPINB4 | ENST00000341074.10 | c.476T>A | p.Ile159Asn | missense_variant | 6/8 | 1 | NM_002974.4 | P1 | |
SERPINB4 | ENST00000413673.5 | c.482T>A | p.Ile161Asn | missense_variant | 5/7 | 1 | |||
SERPINB4 | ENST00000436264.1 | c.347T>A | p.Ile116Asn | missense_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455906Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724214
GnomAD4 exome
AF:
AC:
1
AN:
1455906
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
724214
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MutPred
Gain of disorder (P = 0.0157);.;
MVP
MPC
ClinPred
D
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