rs62653604
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000288.4(PEX7):c.334C>T(p.Gln112*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
PEX7
NM_000288.4 stop_gained
NM_000288.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 5.32
Genes affected
PEX7 (HGNC:8860): (peroxisomal biogenesis factor 7) This gene encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Defects in this gene cause peroxisome biogenesis disorders (PBDs), which are characterized by multiple defects in peroxisome function. There are at least 14 complementation groups for PBDs, with more than one phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene have been associated with PBD complementation group 11 (PBD-CG11) disorders, rhizomelic chondrodysplasia punctata type 1 (RCDP1), and Refsum disease (RD). [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-136826464-C-T is Pathogenic according to our data. Variant chr6-136826464-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 371661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-136826464-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PEX7 | NM_000288.4 | c.334C>T | p.Gln112* | stop_gained | 3/10 | ENST00000318471.5 | NP_000279.1 | |
PEX7 | NM_001410945.1 | c.220C>T | p.Gln74* | stop_gained | 3/10 | NP_001397874.1 | ||
PEX7 | XM_006715502.3 | c.334C>T | p.Gln112* | stop_gained | 3/7 | XP_006715565.1 | ||
PEX7 | XM_047418874.1 | c.334C>T | p.Gln112* | stop_gained | 3/6 | XP_047274830.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PEX7 | ENST00000318471.5 | c.334C>T | p.Gln112* | stop_gained | 3/10 | 1 | NM_000288.4 | ENSP00000315680.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Peroxisome biogenesis disorder 9B Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 04, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 28, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 371661). This variant is also known as 339C>T. This premature translational stop signal has been observed in individual(s) with Rhizomelic Chondrodysplasia Punctata (PMID: 12325024). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln112*) in the PEX7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX7 are known to be pathogenic (PMID: 12325024, 12522768, 20301447). - |
Rhizomelic chondrodysplasia punctata type 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 10, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at