rs1553496202
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting
The NM_006267.5(RANBP2):c.4997_4999del(p.Glu1666del) variant causes a inframe deletion change. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 11)
Consequence
RANBP2
NM_006267.5 inframe_deletion
NM_006267.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.36
Genes affected
RANBP2 (HGNC:9848): (RAN binding protein 2) RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_006267.5. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RANBP2 | NM_006267.5 | c.4997_4999del | p.Glu1666del | inframe_deletion | 20/29 | ENST00000283195.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.4997_4999del | p.Glu1666del | inframe_deletion | 20/29 | 1 | NM_006267.5 | P1 | |
RANBP2 | ENST00000697737.1 | c.2603-6165_2603-6163del | intron_variant | ||||||
RANBP2 | ENST00000697740.1 | c.2525-6165_2525-6163del | intron_variant |
Frequencies
GnomAD3 genomes ? Cov.: 11
GnomAD3 genomes
?
Cov.:
11
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 11
GnomAD4 genome
?
Cov.:
11
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial acute necrotizing encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | 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. ClinVar contains an entry for this variant (Variation ID: 469466). This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.4997_4999del, results in the deletion of 1 amino acid(s) of the RANBP2 protein (p.Glu1666del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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