rs398123305
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000287.4(PEX6):βc.689_690delβ(p.Glu230ValfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. E230E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000287.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX6 | NM_000287.4 | c.689_690del | p.Glu230ValfsTer11 | frameshift_variant | 1/17 | ENST00000304611.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX6 | ENST00000304611.13 | c.689_690del | p.Glu230ValfsTer11 | frameshift_variant | 1/17 | 1 | NM_000287.4 | P1 | |
PEX6 | ENST00000244546.4 | c.689_690del | p.Glu230ValfsTer11 | frameshift_variant | 1/15 | 1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461894Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Heimler syndrome 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 07, 2022 | - - |
Peroxisome biogenesis disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2022 | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with PEX6-related conditions (PMID: 19877282). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu230Valfs*11) 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
Publications
No publications associated with this variant yet.