rs116692495
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003630.3(PEX3):c.-4A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000939 in 1,610,084 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00061 ( 4 hom. )
Consequence
PEX3
NM_003630.3 5_prime_UTR
NM_003630.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.780
Genes affected
PEX3 (HGNC:8858): (peroxisomal biogenesis factor 3) The product of this gene is involved in peroxisome biosynthesis and integrity. It assembles membrane vesicles before the matrix proteins are translocated. 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 Zellweger syndrome (ZWS). [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=-0.63).
BP6
?
Variant 6-143451039-A-G is Benign according to our data. Variant chr6-143451039-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 259104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00408 (621/152250) while in subpopulation AFR AF= 0.0131 (543/41540). AF 95% confidence interval is 0.0122. There are 5 homozygotes in gnomad4. There are 288 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX3 | NM_003630.3 | c.-4A>G | 5_prime_UTR_variant | 1/12 | ENST00000367591.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX3 | ENST00000367591.5 | c.-4A>G | 5_prime_UTR_variant | 1/12 | 1 | NM_003630.3 | P1 | ||
PEX3 | ENST00000367592.5 | c.-4A>G | 5_prime_UTR_variant | 1/7 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00407 AC: 619AN: 152132Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00120 AC: 301AN: 251466Hom.: 3 AF XY: 0.000905 AC XY: 123AN XY: 135918
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GnomAD4 exome AF: 0.000611 AC: 891AN: 1457834Hom.: 4 Cov.: 30 AF XY: 0.000566 AC XY: 411AN XY: 725586
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GnomAD4 genome ? AF: 0.00408 AC: 621AN: 152250Hom.: 5 Cov.: 32 AF XY: 0.00387 AC XY: 288AN XY: 74446
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Peroxisome biogenesis disorder 10A (Zellweger) Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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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