rs1057516882
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000288.4(PEX7):c.60C>G(p.Tyr20Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Y20Y) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Consequence
PEX7
NM_000288.4 stop_gained
NM_000288.4 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 0.207
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 does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 91 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-136822725-C-G is Pathogenic according to our data. Variant chr6-136822725-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 370938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEX7 | NM_000288.4 | c.60C>G | p.Tyr20Ter | stop_gained | 1/10 | ENST00000318471.5 | |
PEX7 | XM_006715502.3 | c.60C>G | p.Tyr20Ter | stop_gained | 1/7 | ||
PEX7 | XM_047418874.1 | c.60C>G | p.Tyr20Ter | stop_gained | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEX7 | ENST00000318471.5 | c.60C>G | p.Tyr20Ter | stop_gained | 1/10 | 1 | NM_000288.4 | P1 | |
PEX7 | ENST00000367756.8 | c.60C>G | p.Tyr20Ter | stop_gained | 1/4 | 3 | |||
PEX7 | ENST00000541292.6 | c.60C>G | p.Tyr20Ter | stop_gained, NMD_transcript_variant | 1/11 | 5 | |||
PEX7 | ENST00000678593.1 | c.60C>G | p.Tyr20Ter | stop_gained, NMD_transcript_variant | 1/8 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Rhizomelic chondrodysplasia punctata type 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 19, 2016 | - - |
Peroxisome biogenesis disorder 9B Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 14, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A
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