NM_001127649.3:c.350C>T
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_001127649.3(PEX26):c.350C>T(p.Pro117Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,008 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P117S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001127649.3 missense
Scores
Clinical Significance
Conservation
Publications
- peroxisome biogenesis disorderInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- peroxisome biogenesis disorder 7A (Zellweger)Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- peroxisome biogenesis disorder 7BInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P
- Zellweger spectrum disordersInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PEX26 | NM_001127649.3 | c.350C>T | p.Pro117Leu | missense_variant | Exon 2 of 5 | ENST00000399744.8 | NP_001121121.1 | |
PEX26 | NM_017929.6 | c.350C>T | p.Pro117Leu | missense_variant | Exon 3 of 6 | NP_060399.1 | ||
PEX26 | NM_001199319.2 | c.350C>T | p.Pro117Leu | missense_variant | Exon 3 of 5 | NP_001186248.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PEX26 | ENST00000399744.8 | c.350C>T | p.Pro117Leu | missense_variant | Exon 2 of 5 | 1 | NM_001127649.3 | ENSP00000382648.4 | ||
PEX26 | ENST00000329627.11 | c.350C>T | p.Pro117Leu | missense_variant | Exon 3 of 6 | 1 | ENSP00000331106.5 | |||
PEX26 | ENST00000428061.2 | c.350C>T | p.Pro117Leu | missense_variant | Exon 2 of 4 | 1 | ENSP00000412441.2 | |||
ENSG00000288683 | ENST00000474897.6 | n.350C>T | non_coding_transcript_exon_variant | Exon 3 of 9 | 5 | ENSP00000434235.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152126Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000795 AC: 2AN: 251470 AF XY: 0.00000736 show subpopulations
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727244 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74310 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 7B;C3888385:Peroxisome biogenesis disorder 7A (Zellweger) Pathogenic:1Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 117 of the PEX26 protein (p.Pro117Leu). This variant is present in population databases (rs61752134, gnomAD 0.01%). This missense change has been observed in individual(s) with infantile Refsum disease (PMID: 15858711). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects PEX26 function (PMID: 16257970). 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. -
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Peroxisome biogenesis disorder 7A (Zellweger) Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at