rs1554375511
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000466.3(PEX1):c.760_761insT(p.Ser254PhefsTer5) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
PEX1
NM_000466.3 frameshift
NM_000466.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.38
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 7-92517754-G-GA is Pathogenic according to our data. Variant chr7-92517754-G-GA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 557794.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.760_761insT | p.Ser254PhefsTer5 | frameshift_variant | 5/24 | ENST00000248633.9 | |
PEX1 | NM_001282677.2 | c.760_761insT | p.Ser254PhefsTer5 | frameshift_variant | 5/23 | ||
PEX1 | NM_001282678.2 | c.136_137insT | p.Ser46PhefsTer5 | frameshift_variant | 5/24 | ||
PEX1 | XM_047420472.1 | c.760_761insT | p.Ser254PhefsTer5 | frameshift_variant | 5/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX1 | ENST00000248633.9 | c.760_761insT | p.Ser254PhefsTer5 | frameshift_variant | 5/24 | 1 | NM_000466.3 | P1 | |
PEX1 | ENST00000428214.5 | c.760_761insT | p.Ser254PhefsTer5 | frameshift_variant | 5/23 | 1 | |||
PEX1 | ENST00000438045.5 | c.274-3788_274-3787insT | intron_variant | 2 | |||||
PEX1 | ENST00000484913.5 | n.799_800insT | non_coding_transcript_exon_variant | 5/24 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Peroxisome biogenesis disorder 1A (Zellweger) Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 11, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at