6-42965078-C-G
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5
The NM_000287.4(PEX6):c.2663G>C(p.Arg888Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R888H) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000287.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX6 | NM_000287.4 | c.2663G>C | p.Arg888Pro | missense_variant | 15/17 | ENST00000304611.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX6 | ENST00000304611.13 | c.2663G>C | p.Arg888Pro | missense_variant | 15/17 | 1 | NM_000287.4 | P1 | |
PEX6 | ENST00000244546.4 | c.*199G>C | 3_prime_UTR_variant | 13/15 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 4A (Zellweger) Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2016 | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM3,PM2,PP3,PP5. - |
Heimler syndrome 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 17, 2022 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 22, 2024 | Variant summary: PEX6 c.2663G>C (p.Arg888Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251478 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2663G>C has been reported in the literature in individuals affected with Zellweger Syndrome. These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 931051). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at