NM_000466.3:c.358-11G>C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000466.3(PEX1):c.358-11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 1,477,148 control chromosomes in the GnomAD database, including 1,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000466.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PEX1 | NM_000466.3 | c.358-11G>C | intron_variant | Intron 3 of 23 | ENST00000248633.9 | NP_000457.1 | ||
PEX1 | NM_001282677.2 | c.358-11G>C | intron_variant | Intron 3 of 22 | NP_001269606.1 | |||
PEX1 | NM_001282678.2 | c.-267-11G>C | intron_variant | Intron 3 of 23 | NP_001269607.1 | |||
PEX1 | XM_047420472.1 | c.358-11G>C | intron_variant | Intron 3 of 22 | XP_047276428.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PEX1 | ENST00000248633.9 | c.358-11G>C | intron_variant | Intron 3 of 23 | 1 | NM_000466.3 | ENSP00000248633.4 | |||
PEX1 | ENST00000428214.5 | c.358-11G>C | intron_variant | Intron 3 of 22 | 1 | ENSP00000394413.1 | ||||
PEX1 | ENST00000438045.5 | c.273+3836G>C | intron_variant | Intron 2 of 20 | 2 | ENSP00000410438.1 | ||||
PEX1 | ENST00000484913.5 | n.397-11G>C | intron_variant | Intron 3 of 23 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0403 AC: 6132AN: 152008Hom.: 153 Cov.: 32
GnomAD3 exomes AF: 0.0334 AC: 8393AN: 251138Hom.: 173 AF XY: 0.0334 AC XY: 4529AN XY: 135748
GnomAD4 exome AF: 0.0380 AC: 50393AN: 1325022Hom.: 1093 Cov.: 21 AF XY: 0.0379 AC XY: 25258AN XY: 666876
GnomAD4 genome AF: 0.0404 AC: 6153AN: 152126Hom.: 155 Cov.: 32 AF XY: 0.0403 AC XY: 2996AN XY: 74362
ClinVar
Submissions by phenotype
not provided Benign:3
Variant summary: The PEX1 c.358-11G>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction the strenghtening of a canonical splice acceptor site site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4339/121280 control chromosomes (85 homozygotes) at a frequency of 0.0357767, which is approximately 9 times the estimated maximal expected allele frequency of a pathogenic PEX1 variant (0.003873), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Zellweger spectrum disorders Benign:2
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not specified Benign:1
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Peroxisome biogenesis disorder 1A (Zellweger) Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at