rs281875368
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_005857.5(ZMPSTE24):c.592_593del(p.Ile198LeufsTer19) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
ZMPSTE24
NM_005857.5 frameshift
NM_005857.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.89
Genes affected
ZMPSTE24 (HGNC:12877): (zinc metallopeptidase STE24) This gene encodes a member of the peptidase M48A family. The encoded protein is a zinc metalloproteinase involved in the two step post-translational proteolytic cleavage of carboxy terminal residues of farnesylated prelamin A to form mature lamin A. Mutations in this gene have been associated with mandibuloacral dysplasia and restrictive dermopathy. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZMPSTE24 | NM_005857.5 | c.592_593del | p.Ile198LeufsTer19 | frameshift_variant | 5/10 | ENST00000372759.4 | |
ZMPSTE24 | XM_047427582.1 | c.343_344del | p.Ile115LeufsTer19 | frameshift_variant | 4/9 | ||
ZMPSTE24 | XM_047427590.1 | c.592_593del | p.Ile198LeufsTer19 | frameshift_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZMPSTE24 | ENST00000372759.4 | c.592_593del | p.Ile198LeufsTer19 | frameshift_variant | 5/10 | 1 | NM_005857.5 | P1 | |
ZMPSTE24 | ENST00000674703.1 | c.*433_*434del | 3_prime_UTR_variant, NMD_transcript_variant | 6/11 | |||||
ZMPSTE24 | ENST00000675754.1 | c.*334_*335del | 3_prime_UTR_variant, NMD_transcript_variant | 6/11 | |||||
ZMPSTE24 | ENST00000675937.1 | c.592_593del | p.Ile198LeufsTer19 | frameshift_variant, NMD_transcript_variant | 5/11 |
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: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not provided Other:1
not provided, no classification provided | literature only | ZMPSTE24 homepage - Leiden Muscular Dystrophy pages | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at