rs1555549855
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000286.3(PEX12):c.460C>T(p.Arg154Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,874 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R154R) has been classified as Likely benign.
Frequency
Consequence
NM_000286.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX12 | NM_000286.3 | c.460C>T | p.Arg154Ter | stop_gained | 2/3 | ENST00000225873.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX12 | ENST00000225873.9 | c.460C>T | p.Arg154Ter | stop_gained | 2/3 | 1 | NM_000286.3 | P1 | |
PEX12 | ENST00000586663.2 | c.460C>T | p.Arg154Ter | stop_gained | 2/3 | 1 | |||
PEX12 | ENST00000585380.1 | c.460C>T | p.Arg154Ter | stop_gained | 3/3 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727238
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 3A (Zellweger) Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 551612). This premature translational stop signal has been observed in individual(s) with Zellweger syndrome spectrum (PMID: 21031596). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg154*) in the PEX12 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX12 are known to be pathogenic (PMID: 9090384, 9632816, 21031596). - |
Peroxisome biogenesis disorder type 3B;C3553929:Peroxisome biogenesis disorder 3A (Zellweger) Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 24, 2017 | - - |
PEX12-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 25, 2023 | The PEX12 c.460C>T variant is predicted to result in premature protein termination (p.Arg154*). This variant was reported in an individual with peroxisome biogenesis disorder 3 (Ebberink et al. 2011. PubMed ID: 21031596). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in PEX12 are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at