1-151399589-T-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 10P and 2B. PVS1PM2BP6_Moderate
The NM_002796.3(PSMB4):āc.2T>Cā(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000111 in 1,609,346 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 benign (ā ).
Frequency
Genomes: š 0.00026 ( 0 hom., cov: 31)
Exomes š: 0.000095 ( 0 hom. )
Consequence
PSMB4
NM_002796.3 start_lost
NM_002796.3 start_lost
Scores
5
5
6
Clinical Significance
Conservation
PhyloP100: 4.11
Genes affected
PSMB4 (HGNC:9541): (proteasome 20S subunit beta 4) 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. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 1-151399589-T-C is Benign according to our data. Variant chr1-151399589-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2971683.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PSMB4 | NM_002796.3 | c.2T>C | p.Met1? | start_lost | 1/7 | ENST00000290541.7 | NP_002787.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PSMB4 | ENST00000290541.7 | c.2T>C | p.Met1? | start_lost | 1/7 | 1 | NM_002796.3 | ENSP00000290541.6 |
Frequencies
GnomAD3 genomes AF: 0.000256 AC: 39AN: 152226Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000215 AC: 53AN: 245986Hom.: 0 AF XY: 0.000187 AC XY: 25AN XY: 133608
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GnomAD4 exome AF: 0.0000954 AC: 139AN: 1457120Hom.: 0 Cov.: 30 AF XY: 0.0000938 AC XY: 68AN XY: 725000
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GnomAD4 genome AF: 0.000256 AC: 39AN: 152226Hom.: 0 Cov.: 31 AF XY: 0.000498 AC XY: 37AN XY: 74366
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 05, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MutPred
Gain of glycosylation at M1 (P = 0.0422);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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