rs62653610
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000288.4(PEX7):c.785C>T(p.Ser262Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000997 in 1,605,324 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S262S) has been classified as Likely benign.
Frequency
Consequence
NM_000288.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX7 | NM_000288.4 | c.785C>T | p.Ser262Leu | missense_variant | 8/10 | ENST00000318471.5 | |
PEX7 | NM_001410945.1 | c.671C>T | p.Ser224Leu | missense_variant | 8/10 | ||
PEX7 | XM_006715502.3 | c.491C>T | p.Ser164Leu | missense_variant | 5/7 | ||
PEX7 | XM_047418874.1 | c.527-25907C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX7 | ENST00000318471.5 | c.785C>T | p.Ser262Leu | missense_variant | 8/10 | 1 | NM_000288.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000674 AC: 1AN: 148416Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248660Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134604
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1456908Hom.: 0 Cov.: 33 AF XY: 0.00000828 AC XY: 6AN XY: 724908
GnomAD4 genome AF: 0.00000674 AC: 1AN: 148416Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1AN XY: 72004
ClinVar
Submissions by phenotype
Rhizomelic chondrodysplasia punctata type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Sep 26, 2017 | - - |
Peroxisome biogenesis disorder 9B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 262 of the PEX7 protein (p.Ser262Leu). This variant is present in population databases (rs62653610, gnomAD 0.006%). This missense change has been observed in individual(s) with rhizomelic chondrodysplasia punctata (PMID: 11781871). ClinVar contains an entry for this variant (Variation ID: 551503). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at