chr22-18078373-CGTTA-C
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001127649.3(PEX26):c.-3_1del variant causes a start lost, 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
PEX26
NM_001127649.3 start_lost, 5_prime_UTR
NM_001127649.3 start_lost, 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.10
Genes affected
PEX26 (HGNC:22965): (peroxisomal biogenesis factor 26) This gene belongs to the peroxin-26 gene family. It is probably required for protein import into peroxisomes. It anchors PEX1 and PEX6 to peroxisome membranes, possibly to form heteromeric AAA ATPase complexes required for the import of proteins into peroxisomes. Defects in this gene are the cause of peroxisome biogenesis disorder complementation group 8 (PBD-CG8). PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX26 | NM_001127649.3 | c.-3_1del | start_lost, 5_prime_UTR_variant | 1/5 | ENST00000399744.8 | ||
PEX26 | NM_001199319.2 | c.-3_1del | start_lost, 5_prime_UTR_variant | 2/5 | |||
PEX26 | NM_017929.6 | c.-3_1del | start_lost, 5_prime_UTR_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX26 | ENST00000399744.8 | c.-3_1del | start_lost, 5_prime_UTR_variant | 1/5 | 1 | NM_001127649.3 | P1 | ||
ENST00000607927.1 | n.508_511del | non_coding_transcript_exon_variant | 1/1 |
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: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Peroxisome biogenesis disorder 7B;C3888385:Peroxisome biogenesis disorder 7A (Zellweger) Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 07, 2021 | This sequence change affects the initiator methionine of the PEX26 mRNA. The next in-frame methionine is located at codon 96. This variant is not present in population databases (ExAC no frequency). Disruption of the initiator codon ‚Äãhas been observed in individual(s) with clinical features of Zellweger spectrum disorder (PMID: 12851857, 28944237). This variant disrupts the initiator methionine in PEX26. If translation initiates from the next in-frame methionine, the PEX26 protein would no longer include the region containing the p.Gly89 amino acid residue. Other variant(s) that disrupt this residue have been observed in individuals with PEX26-related conditions (PMID: 12851857), which suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.