chr1-151399625-C-CG
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002796.3(PSMB4):c.44dup(p.Pro16SerfsTer45) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,544 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A13A) has been classified as Likely benign.
Frequency
Consequence
NM_002796.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSMB4 | NM_002796.3 | c.44dup | p.Pro16SerfsTer45 | frameshift_variant | 1/7 | ENST00000290541.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSMB4 | ENST00000290541.7 | c.44dup | p.Pro16SerfsTer45 | frameshift_variant | 1/7 | 1 | NM_002796.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249810Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135496
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461400Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 726978
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152144Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
Proteasome-associated autoinflammatory syndrome 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 23, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 05, 2022 | This premature translational stop signal has been observed in individual(s) with clinical features of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome (PMID: 26524591). This sequence change creates a premature translational stop signal (p.Pro16Serfs*45) in the PSMB4 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in PSMB4 cause disease. This variant is present in population databases (no rsID available, gnomAD 0.006%). ClinVar contains an entry for this variant (Variation ID: 548957). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at