rs61752092
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_002617.4(PEX10):c.730C>T(p.Arg244*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,456,660 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_002617.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PEX10 | NM_002617.4 | c.730C>T | p.Arg244* | stop_gained | 4/6 | ENST00000447513.7 | NP_002608.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PEX10 | ENST00000447513.7 | c.730C>T | p.Arg244* | stop_gained | 4/6 | 1 | NM_002617.4 | ENSP00000407922.2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.0000253 AC: 6AN: 237538Hom.: 0 AF XY: 0.0000385 AC XY: 5AN XY: 129914
GnomAD4 exome AF: 0.00000618 AC: 9AN: 1456660Hom.: 0 Cov.: 35 AF XY: 0.00000828 AC XY: 6AN XY: 724288
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 6A (Zellweger) Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 13, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 18, 2023 | - - |
Peroxisome biogenesis disorder 6B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2010 | - - |
Peroxisome biogenesis disorder 6A (Zellweger);C3553948:Peroxisome biogenesis disorder 6B Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 04, 2017 | - - |
Peroxisome biogenesis disorder, complementation group 7 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 18, 2023 | This sequence change creates a premature translational stop signal (p.Arg264*) in the PEX10 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX10 are known to be pathogenic (PMID: 9683594, 10862081, 21031596). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with peroxisomal biogenesis disorders (PMID: 15542397, 17041890, 19105186, 20695019, 27230853). This variant is also known as p.Arg244*. ClinVar contains an entry for this variant (Variation ID: 162435). For these reasons, this variant has been classified as Pathogenic. - |
Zellweger spectrum disorders Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 21, 2021 | - - |
Peroxisome biogenesis disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 09, 2022 | Variant summary: PEX10 c.790C>T (p.Arg264X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2.5e-05 in 237538 control chromosomes (gnomAD). c.790C>T has been reported in the literature in individuals affected with Zellweger Syndrome, including one homozygote (Steinberg_2004, Krause_2006), and peroxisomal biogenesis disorder (Regal_2010). These data indicate that the variant is likely to be associated with disease. One publication reports that the variant may induce nonsense mediated decay as cDNA could not be recovered from homozygotic fibroblasts and only the second variant allele could be recovered from compound heterozygotic cells (Krause_2006). Three ClinVar submitters have assessed the variant since 2014: all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at