rs535271603
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000248633.9(PEX1):c.2843G>A(p.Arg948Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000657 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R948W) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000248633.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PEX1 | NM_000466.3 | c.2843G>A | p.Arg948Gln | missense_variant | 18/24 | ENST00000248633.9 | NP_000457.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PEX1 | ENST00000248633.9 | c.2843G>A | p.Arg948Gln | missense_variant | 18/24 | 1 | NM_000466.3 | ENSP00000248633 | P1 | |
ENST00000658444.1 | n.3902C>T | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251322Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135836
GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461700Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 49AN XY: 727162
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74416
ClinVar
Submissions by phenotype
Zellweger spectrum disorders Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 948 of the PEX1 protein (p.Arg948Gln). This variant is present in population databases (rs535271603, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of peroxisome biogenesis disorders (PMID: 19105186). ClinVar contains an entry for this variant (Variation ID: 441031). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PEX1 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Peroxisome biogenesis disorder 1B;C4551980:Heimler syndrome 1;C4721541:Peroxisome biogenesis disorder 1A (Zellweger) Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 15, 2021 | - - |
Peroxisome biogenesis disorder 1A (Zellweger) Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Oct 24, 2017 | - - |
Peroxisome biogenesis disorder 1B;C4721541:Peroxisome biogenesis disorder 1A (Zellweger) Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at