rs1010184002
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000287.4(PEX6):c.273G>A(p.Trp91*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 1,490,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000287.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PEX6 | NM_000287.4 | c.273G>A | p.Trp91* | stop_gained | 1/17 | ENST00000304611.13 | NP_000278.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PEX6 | ENST00000304611.13 | c.273G>A | p.Trp91* | stop_gained | 1/17 | 1 | NM_000287.4 | ENSP00000303511.8 | ||
PEX6 | ENST00000244546.4 | c.273G>A | p.Trp91* | stop_gained | 1/15 | 1 | ENSP00000244546.4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000247 AC: 33AN: 1338634Hom.: 0 Cov.: 36 AF XY: 0.0000227 AC XY: 15AN XY: 660456
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74318
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 4B Pathogenic:2
Likely pathogenic, no assertion criteria provided | clinical testing | Counsyl | Jan 12, 2018 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Sep 06, 2018 | - - |
Heimler syndrome 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | May 08, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 06, 2016 | - - |
Peroxisome biogenesis disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 17, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 498713). This variant has not been reported in the literature in individuals affected with PEX6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp91*) in the PEX6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX6 are known to be pathogenic (PMID: 8670792, 19877282, 21031596). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at