chr2-108735652-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_006267.5(RANBP2):c.526C>T(p.Arg176Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,597,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006267.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000377 AC: 9AN: 238560Hom.: 0 AF XY: 0.0000462 AC XY: 6AN XY: 129854
GnomAD4 exome AF: 0.0000221 AC: 32AN: 1445252Hom.: 0 Cov.: 34 AF XY: 0.0000222 AC XY: 16AN XY: 719350
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74476
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.526C>T (p.R176C) alteration is located in exon 5 (coding exon 5) of the RANBP2 gene. This alteration results from a C to T substitution at nucleotide position 526, causing the arginine (R) at amino acid position 176 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Familial acute necrotizing encephalopathy Uncertain:1
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 missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 537222). This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. This variant is present in population databases (rs543844917, gnomAD 0.04%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 176 of the RANBP2 protein (p.Arg176Cys). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at