rs786205556
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001127649.3(PEX26):c.228C>T(p.Gly76=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001127649.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX26 | NM_001127649.3 | c.228C>T | p.Gly76= | splice_region_variant, synonymous_variant | 1/5 | ENST00000399744.8 | |
PEX26 | NM_017929.6 | c.228C>T | p.Gly76= | splice_region_variant, synonymous_variant | 2/6 | ||
PEX26 | NM_001199319.2 | c.228C>T | p.Gly76= | splice_region_variant, synonymous_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX26 | ENST00000399744.8 | c.228C>T | p.Gly76= | splice_region_variant, synonymous_variant | 1/5 | 1 | NM_001127649.3 | P1 | |
ENST00000607927.1 | n.281G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.91e-7 AC: 1AN: 1446322Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 718834
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 7A (Zellweger) Pathogenic:1Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | 3billion | Jan 03, 2022 | The variant has been reported to be associated with PEX26 related disorder (ClinVar ID: VCV000191169, PMID:27124789).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000000, PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, Cologne University | Nov 22, 2022 | - - |
Uncertain significance, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 17, 2024 | - - |
not provided Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | PEX26: PM2, PP3, PS3:Supporting - |
Likely pathogenic, criteria provided, single submitter | research | Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre | - | - - |
Peroxisome biogenesis disorder 7B;C3888385:Peroxisome biogenesis disorder 7A (Zellweger) Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Studies have shown that this variant results in skipping of 4 nucleotides in the transcript and introduces a premature termination codon (PMID: 32552793). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 191169). This variant has not been reported in the literature in individuals affected with PEX26-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 76 of the PEX26 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PEX26 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at