rs780185468
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_006267.5(RANBP2):c.914_916delGTA(p.Ser305del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,597,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
RANBP2
NM_006267.5 disruptive_inframe_deletion
NM_006267.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0640
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 Likely_benign. Variant got -3 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_006267.5. Strenght limited to Supporting due to length of the change: 1aa.
BS2
High AC in GnomAdExome4 at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RANBP2 | NM_006267.5 | c.914_916delGTA | p.Ser305del | disruptive_inframe_deletion | 7/29 | ENST00000283195.11 | NP_006258.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.914_916delGTA | p.Ser305del | disruptive_inframe_deletion | 7/29 | 1 | NM_006267.5 | ENSP00000283195.6 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000838 AC: 20AN: 238568Hom.: 0 AF XY: 0.0000693 AC XY: 9AN XY: 129856
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GnomAD4 exome AF: 0.0000187 AC: 27AN: 1445234Hom.: 0 AF XY: 0.0000167 AC XY: 12AN XY: 719340
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74374
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Mar 10, 2020 | 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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. This variant has not been reported in the literature in individuals with RANBP2-related disease. This variant is present in population databases (rs780185468, ExAC 0.04%). This variant, c.914_916delGTA, results in the deletion of 1 amino acid of the RANBP2 protein (p.Ser305del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at