2-108730776-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS2_Supporting
The NM_006267.5(RANBP2):c.143A>T(p.Tyr48Phe) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,458,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006267.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000286 AC: 7AN: 245036Hom.: 0 AF XY: 0.0000451 AC XY: 6AN XY: 133086
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1458612Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 725630
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial acute necrotizing encephalopathy Uncertain:1
This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 48 of the RANBP2 protein (p.Tyr48Phe). This variant is present in population databases (rs780017280, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1024410). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at