rs1555257073
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_015932.6(POMP):c.334_335del(p.Ile112TrpfsTer3) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Consequence
POMP
NM_015932.6 frameshift
NM_015932.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.49
Genes affected
POMP (HGNC:20330): (proteasome maturation protein) The protein encoded by this gene is a molecular chaperone that binds 20S preproteasome components and is essential for 20S proteasome formation. The 20S proteasome is the proteolytically active component of the 26S proteasome complex. The encoded protein is degraded before the maturation of the 20S proteasome is complete. A variant in the 5' UTR of this gene has been associated with KLICK syndrome, a rare skin disorder.[provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.218 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 13-28672406-CTA-C is Pathogenic according to our data. Variant chr13-28672406-CTA-C is described in ClinVar as [Pathogenic]. Clinvar id is 522801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMP | NM_015932.6 | c.334_335del | p.Ile112TrpfsTer3 | frameshift_variant | 5/6 | ENST00000380842.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMP | ENST00000380842.5 | c.334_335del | p.Ile112TrpfsTer3 | frameshift_variant | 5/6 | 1 | NM_015932.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Proteasome-associated autoinflammatory syndrome 2 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Feb 14, 2017 | This frameshift mutation is categorized as deleterious according to ACMG guidelines (PMID: 18414213) and was found de novo in a 2-year-old male with seizure-like movements, B-lymphocyte immunodeficiency, thrombocytopenia, anemia, eosinophilia, hypogammaglobulinemia, dermatosis, and skin anomalies suggestive of Sweet syndrome. This individual has been reported in PMID: 29805043 (individual B). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 17, 2018 | - - |
Keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 12, 2023 | - - |
Computational scores
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Calibrated prediction
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Prediction
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