1-2412502-T-C
Variant summary
Our verdict is Pathogenic. Variant got 20 ACMG points: 20P and 0B. PVS1PS1_ModeratePM2PP5_Very_Strong
The NM_002617.4(PEX10):āc.1A>Gā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,360,508 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 Likely pathogenic (ā ā ).
Frequency
Consequence
NM_002617.4 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PEX10 | NM_002617.4 | c.1A>G | p.Met1? | start_lost | Exon 1 of 6 | ENST00000447513.7 | NP_002608.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151938Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000993 AC: 12AN: 1208570Hom.: 0 Cov.: 31 AF XY: 0.00000678 AC XY: 4AN XY: 590018
GnomAD4 genome AF: 0.0000329 AC: 5AN: 151938Hom.: 0 Cov.: 34 AF XY: 0.0000539 AC XY: 4AN XY: 74246
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 6A (Zellweger);C3553948:Peroxisome biogenesis disorder 6B Pathogenic:2
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Peroxisome biogenesis disorder 6A (Zellweger) Pathogenic:1
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Zellweger spectrum disorders Pathogenic:1
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Peroxisome biogenesis disorder, complementation group 7 Pathogenic:1
This sequence change affects the initiator methionine of the PEX10 mRNA. The next in-frame methionine is located at codon 145. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with clinical features of Zellweger spectrum disorder (PMID: 25179809, 28320181). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 280002). For these reasons, this variant has been classified as Pathogenic. -
not provided Pathogenic:1
Initiation codon variant in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35038753, 37994247, 28857144, 25179809) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at