rs375272295
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001351132.2(PEX5):c.1718+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000588 in 1,613,962 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00062 ( 2 hom. )
Consequence
PEX5
NM_001351132.2 intron
NM_001351132.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.50
Genes affected
PEX5 (HGNC:9719): (peroxisomal biogenesis factor 5) The product of this gene binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. The peroxisomal biogenesis disorders are a heterogeneous group with at least 14 complementation groups and with more than 1 phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause of neonatal adrenoleukodystrophy (NALD), a cause of Zellweger syndrome (ZWS) as well as may be a cause of infantile Refsum disease (IRD). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 12-7209857-A-G is Benign according to our data. Variant chr12-7209857-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000618 (903/1461754) while in subpopulation NFE AF= 0.00078 (867/1111902). AF 95% confidence interval is 0.000736. There are 2 homozygotes in gnomad4_exome. There are 408 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX5 | NM_001351132.2 | c.1718+17A>G | intron_variant | ENST00000675855.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX5 | ENST00000675855.1 | c.1718+17A>G | intron_variant | NM_001351132.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000302 AC: 46AN: 152208Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000286 AC: 72AN: 251328Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135872
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GnomAD4 exome AF: 0.000618 AC: 903AN: 1461754Hom.: 2 Cov.: 34 AF XY: 0.000561 AC XY: 408AN XY: 727184
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GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74380
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Peroxisome biogenesis disorder 2B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at