rs763497305
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006267.5(RANBP2):āc.2469A>Gā(p.Lys823Lys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,611,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_006267.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RANBP2 | NM_006267.5 | c.2469A>G | p.Lys823Lys | splice_region_variant, synonymous_variant | 18/29 | ENST00000283195.11 | NP_006258.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.2469A>G | p.Lys823Lys | splice_region_variant, synonymous_variant | 18/29 | 1 | NM_006267.5 | ENSP00000283195.6 | ||
RANBP2 | ENST00000697737.1 | c.2469A>G | p.Lys823Lys | splice_region_variant, synonymous_variant | 18/27 | ENSP00000513426.1 | ||||
RANBP2 | ENST00000697740.1 | c.2391A>G | p.Lys797Lys | splice_region_variant, synonymous_variant | 18/27 | ENSP00000513427.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 31
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459672Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 726132
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74306
ClinVar
Submissions by phenotype
Familial acute necrotizing encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 12, 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 583133). 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 sequence change affects codon 823 of the RANBP2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RANBP2 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at