rs757852291
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000318471.5(PEX7):c.86C>T(p.Pro29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000296 in 1,488,770 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. P29A) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000318471.5 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 |
---|---|---|---|---|---|---|---|---|
PEX7 | NM_000288.4 | c.86C>T | p.Pro29Leu | missense_variant | 1/10 | ENST00000318471.5 | NP_000279.1 | |
PEX7 | XM_006715502.3 | c.86C>T | p.Pro29Leu | missense_variant | 1/7 | XP_006715565.1 | ||
PEX7 | XM_047418874.1 | c.86C>T | p.Pro29Leu | missense_variant | 1/6 | XP_047274830.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PEX7 | ENST00000318471.5 | c.86C>T | p.Pro29Leu | missense_variant | 1/10 | 1 | NM_000288.4 | ENSP00000315680 | P1 | |
PEX7 | ENST00000367756.8 | c.86C>T | p.Pro29Leu | missense_variant | 1/4 | 3 | ENSP00000356730 | |||
PEX7 | ENST00000541292.6 | c.86C>T | p.Pro29Leu | missense_variant, NMD_transcript_variant | 1/11 | 5 | ENSP00000441004 | |||
PEX7 | ENST00000678593.1 | c.86C>T | p.Pro29Leu | missense_variant, NMD_transcript_variant | 1/8 | ENSP00000503841 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151960Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000337 AC: 3AN: 89132Hom.: 0 AF XY: 0.0000593 AC XY: 3AN XY: 50574
GnomAD4 exome AF: 0.0000292 AC: 39AN: 1336702Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 20AN XY: 659500
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152068Hom.: 0 Cov.: 35 AF XY: 0.0000403 AC XY: 3AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 01, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 24, 2016 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 26, 2021 | The c.86C>T (p.P29L) alteration is located in exon 1 (coding exon 1) of the PEX7 gene. This alteration results from a C to T substitution at nucleotide position 86, causing the proline (P) at amino acid position 29 to be replaced by a leucine (L). The in silico prediction for the p.P29L alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Phytanic acid storage disease;C1859133:Rhizomelic chondrodysplasia punctata type 1;C2749346:Peroxisome biogenesis disorder 9B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Peroxisome biogenesis disorder 9B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 15, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 29 of the PEX7 protein (p.Pro29Leu). This variant is present in population databases (rs757852291, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PEX7-related conditions. ClinVar contains an entry for this variant (Variation ID: 498141). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Rhizomelic chondrodysplasia punctata Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at