chr1-2405815-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_002617.4(PEX10):c.932G>A(p.Arg311Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000875 in 1,599,512 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R311G) has been classified as Uncertain significance.
Frequency
Consequence
NM_002617.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX10 | NM_002617.4 | c.932G>A | p.Arg311Gln | missense_variant | 6/6 | ENST00000447513.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX10 | ENST00000447513.7 | c.932G>A | p.Arg311Gln | missense_variant | 6/6 | 1 | NM_002617.4 | P4 | |
PEX10 | ENST00000288774.8 | c.992G>A | p.Arg331Gln | missense_variant | 6/6 | 1 | |||
PEX10 | ENST00000507596.5 | c.926G>A | p.Arg309Gln | missense_variant | 6/6 | 5 | A1 | ||
PEX10 | ENST00000650293.1 | c.887G>A | p.Arg296Gln | missense_variant, NMD_transcript_variant | 6/8 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152256Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000136 AC: 3AN: 220654Hom.: 0 AF XY: 0.00000837 AC XY: 1AN XY: 119442
GnomAD4 exome AF: 0.00000691 AC: 10AN: 1447256Hom.: 0 Cov.: 31 AF XY: 0.00000696 AC XY: 5AN XY: 718522
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152256Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74396
ClinVar
Submissions by phenotype
Peroxisome biogenesis disorder 6A (Zellweger) Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 02, 2024 | - - |
Peroxisome biogenesis disorder 6B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2010 | - - |
Peroxisome biogenesis disorder, complementation group 7 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 331 of the PEX10 protein (p.Arg331Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with Zellweger Syndrome Spectrum (PMID: 20695019, 27230853). It has also been observed to segregate with disease in related individuals. This variant is also known as c.932G>A, p.Arg311Gln. ClinVar contains an entry for this variant (Variation ID: 162433). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Peroxisome biogenesis disorder 6A (Zellweger);C3553948:Peroxisome biogenesis disorder 6B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Oct 18, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 08, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at