1-2406566-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_002617.4(PEX10):āc.830T>Cā(p.Leu277Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,048 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). Synonymous variant affecting the same amino acid position (i.e. L277L) has been classified as Likely benign.
Frequency
Consequence
NM_002617.4 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 |
---|---|---|---|---|---|---|---|
PEX10 | NM_002617.4 | c.830T>C | p.Leu277Pro | missense_variant | 5/6 | ENST00000447513.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX10 | ENST00000447513.7 | c.830T>C | p.Leu277Pro | missense_variant | 5/6 | 1 | NM_002617.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461048Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726864
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 6A (Zellweger) Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 03, 2024 | - - |
Peroxisome biogenesis disorder 6B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2009 | - - |
Peroxisome biogenesis disorder, complementation group 7 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 297 of the PEX10 protein (p.Leu297Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with peroxisomal biogenesis disorders (PMID: 19127411, 30640048). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 162432). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects PEX10 function (PMID: 26319495). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 17, 2022 | - - |
Peroxisome biogenesis disorder 6A (Zellweger);C3553948:Peroxisome biogenesis disorder 6B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 08, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at