chr7-92494496-C-CTT
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000466.3(PEX1):c.2916_2917insAA(p.Gly973LysfsTer17) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PEX1
NM_000466.3 frameshift
NM_000466.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.94
Genes affected
PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 7-92494496-C-CTT is Pathogenic according to our data. Variant chr7-92494496-C-CTT is described in ClinVar as [Pathogenic]. Clinvar id is 2013179.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX1 | NM_000466.3 | c.2916_2917insAA | p.Gly973LysfsTer17 | frameshift_variant | 18/24 | ENST00000248633.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX1 | ENST00000248633.9 | c.2916_2917insAA | p.Gly973LysfsTer17 | frameshift_variant | 18/24 | 1 | NM_000466.3 | P1 | |
ENST00000658444.1 | n.3829_3830dup | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251336Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135828
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461490Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727084
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Zellweger spectrum disorders Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 02, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PEX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly973Lysfs*17) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596, 26387595, 31831025). - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at