rs281875372
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000372759.4(ZMPSTE24):c.1020G>A(p.Trp340Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000372759.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZMPSTE24 | NM_005857.5 | c.1020G>A | p.Trp340Ter | stop_gained | 8/10 | ENST00000372759.4 | NP_005848.2 | |
ZMPSTE24 | XM_047427582.1 | c.771G>A | p.Trp257Ter | stop_gained | 7/9 | XP_047283538.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZMPSTE24 | ENST00000372759.4 | c.1020G>A | p.Trp340Ter | stop_gained | 8/10 | 1 | NM_005857.5 | ENSP00000361845 | P1 | |
ZMPSTE24 | ENST00000674703.1 | c.*861G>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | ENSP00000501674 | |||||
ZMPSTE24 | ENST00000675754.1 | c.*762G>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | ENSP00000502555 | |||||
ZMPSTE24 | ENST00000675937.1 | c.*265G>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | ENSP00000502683 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251456Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135910
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461782Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727188
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:1Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 17, 2023 | This sequence change creates a premature translational stop signal (p.Trp340*) in the ZMPSTE24 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZMPSTE24 are known to be pathogenic (PMID: 22718200, 24169522). This variant is present in population databases (rs281875372, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with restrictive dermopathy (PMID: 21108632). ClinVar contains an entry for this variant (Variation ID: 140509). For these reasons, this variant has been classified as Pathogenic. - |
not provided, no classification provided | literature only | ZMPSTE24 homepage - Leiden Muscular Dystrophy pages | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at