rs369359789
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_002800.5(PSMB9):c.494G>A(p.Gly165Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,612,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
PSMB9
NM_002800.5 missense
NM_002800.5 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 3.89
Genes affected
PSMB9 (HGNC:9546): (proteasome 20S subunit beta 9) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-32858467-G-A is Pathogenic according to our data. Variant chr6-32858467-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 548995.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32858467-G-A is described in UniProt as null. Variant chr6-32858467-G-A is described in UniProt as null. Variant chr6-32858467-G-A is described in UniProt as null. Variant chr6-32858467-G-A is described in UniProt as null. Variant chr6-32858467-G-A is described in UniProt as null. Variant chr6-32858467-G-A is described in UniProt as null. Variant chr6-32858467-G-A is described in UniProt as null.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26273108). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSMB9 | NM_002800.5 | c.494G>A | p.Gly165Asp | missense_variant | 5/6 | ENST00000374859.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSMB9 | ENST00000374859.3 | c.494G>A | p.Gly165Asp | missense_variant | 5/6 | 1 | NM_002800.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000406 AC: 10AN: 246572Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134412
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1460736Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726676
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GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74350
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Proteasome-associated autoinflammatory syndrome 3 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | May 14, 2024 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | May 27, 2022 | ACMG classification criteria: PS4 supporting, PM1 moderated, PM2 moderated, PM3 supporting, BP4 supporting - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.0040
.;B
Vest4
MVP
MPC
0.53
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at