rs536486149
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002617.4(PEX10):c.640C>T(p.Arg214Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000764 in 1,609,572 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R214H) has been classified as Uncertain significance.
Frequency
Consequence
NM_002617.4 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 |
---|---|---|---|---|---|---|---|---|
PEX10 | NM_002617.4 | c.640C>T | p.Arg214Cys | missense_variant | 4/6 | ENST00000447513.7 | NP_002608.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152236Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000627 AC: 15AN: 239380Hom.: 0 AF XY: 0.000100 AC XY: 13AN XY: 130042
GnomAD4 exome AF: 0.0000782 AC: 114AN: 1457218Hom.: 1 Cov.: 35 AF XY: 0.0000801 AC XY: 58AN XY: 724542
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152354Hom.: 0 Cov.: 34 AF XY: 0.0000671 AC XY: 5AN XY: 74492
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 09, 2021 | The c.700C>T (p.R234C) alteration is located in exon 4 (coding exon 4) of the PEX10 gene. This alteration results from a C to T substitution at nucleotide position 700, causing the arginine (R) at amino acid position 234 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Peroxisome biogenesis disorder, complementation group 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 234 of the PEX10 protein (p.Arg234Cys). This variant is present in population databases (rs536486149, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PEX10-related conditions. ClinVar contains an entry for this variant (Variation ID: 446046). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Zellweger spectrum disorders Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 05, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at