22-18078393-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001127649.3(PEX26):c.17C>T(p.Ser6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,447,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S6S) has been classified as Likely benign.
Frequency
Consequence
NM_001127649.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX26 | NM_001127649.3 | c.17C>T | p.Ser6Leu | missense_variant | 1/5 | ENST00000399744.8 | |
PEX26 | NM_017929.6 | c.17C>T | p.Ser6Leu | missense_variant | 2/6 | ||
PEX26 | NM_001199319.2 | c.17C>T | p.Ser6Leu | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX26 | ENST00000399744.8 | c.17C>T | p.Ser6Leu | missense_variant | 1/5 | 1 | NM_001127649.3 | P1 | |
ENST00000607927.1 | n.492G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000462 AC: 1AN: 216496Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 119554
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1447912Hom.: 0 Cov.: 30 AF XY: 0.00000417 AC XY: 3AN XY: 719668
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 7B;C3888385:Peroxisome biogenesis disorder 7A (Zellweger) Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PEX26-related conditions. This sequence change replaces serine with leucine at codon 6 of the PEX26 protein (p.Ser6Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at