1-151399579-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002796.3(PSMB4):c.-9G>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.002 in 1,599,106 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002796.3 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PSMB4 | NM_002796.3 | c.-9G>A | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 7 | ENST00000290541.7 | NP_002787.2 | ||
PSMB4 | NM_002796.3 | c.-9G>A | 5_prime_UTR_variant | Exon 1 of 7 | ENST00000290541.7 | NP_002787.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PSMB4 | ENST00000290541 | c.-9G>A | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 7 | 1 | NM_002796.3 | ENSP00000290541.6 | |||
PSMB4 | ENST00000290541 | c.-9G>A | 5_prime_UTR_variant | Exon 1 of 7 | 1 | NM_002796.3 | ENSP00000290541.6 |
Frequencies
GnomAD3 genomes AF: 0.00137 AC: 208AN: 152192Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.000996 AC: 236AN: 237036Hom.: 0 AF XY: 0.00107 AC XY: 138AN XY: 129264
GnomAD4 exome AF: 0.00207 AC: 2992AN: 1446914Hom.: 6 Cov.: 30 AF XY: 0.00201 AC XY: 1445AN XY: 719866
GnomAD4 genome AF: 0.00137 AC: 208AN: 152192Hom.: 1 Cov.: 31 AF XY: 0.00130 AC XY: 97AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:3
BP4, BP7, PS3_moderate -
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This variant occurs in a non-coding region of the PSMB4 gene. It does not change the encoded amino acid sequence of the PSMB4 protein. This variant is present in population databases (rs200946642, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has been observed in individual(s) with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome (PMID: 26524591). ClinVar contains an entry for this variant (Variation ID: 548956). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects PSMB4 function (PMID: 26524591). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Proteasome-associated autoinflammatory syndrome 3 Pathogenic:1Uncertain:1
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PSMB4-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at