rs61752130
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001127649.3(PEX26):c.37_38del(p.Arg13GlyfsTer101) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,594,592 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R13R) has been classified as Likely benign.
Frequency
Consequence
NM_001127649.3 frameshift
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 | UniProt |
---|---|---|---|---|---|---|---|
PEX26 | NM_001127649.3 | c.37_38del | p.Arg13GlyfsTer101 | frameshift_variant | 1/5 | ENST00000399744.8 | |
PEX26 | NM_001199319.2 | c.37_38del | p.Arg13GlyfsTer101 | frameshift_variant | 2/5 | ||
PEX26 | NM_017929.6 | c.37_38del | p.Arg13GlyfsTer101 | frameshift_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX26 | ENST00000399744.8 | c.37_38del | p.Arg13GlyfsTer101 | frameshift_variant | 1/5 | 1 | NM_001127649.3 | P1 | |
ENST00000607927.1 | n.471_472del | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152108Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.93e-7 AC: 1AN: 1442484Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 716636
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74284
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 7B;C3888385:Peroxisome biogenesis disorder 7A (Zellweger) Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 09, 2023 | This sequence change creates a premature translational stop signal (p.Arg13Glyfs*101) in the PEX26 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX26 are known to be pathogenic (PMID: 12851857, 21031596). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Zellweger spectrum disorder (PMID: 15542397). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at