chr2-108764121-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBS2_Supporting
The NM_006267.5(RANBP2):c.3582C>A(p.Phe1194Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RANBP2 | NM_006267.5 | c.3582C>A | p.Phe1194Leu | missense_variant | 20/29 | ENST00000283195.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.3582C>A | p.Phe1194Leu | missense_variant | 20/29 | 1 | NM_006267.5 | P1 | |
RANBP2 | ENST00000697737.1 | c.2602+5573C>A | intron_variant | ||||||
RANBP2 | ENST00000697740.1 | c.2524+5573C>A | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251274Hom.: 0 AF XY: 0.0000884 AC XY: 12AN XY: 135786
GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461816Hom.: 0 Cov.: 34 AF XY: 0.0000344 AC XY: 25AN XY: 727200
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74424
ClinVar
Submissions by phenotype
Familial acute necrotizing encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2019 | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant is present in population databases (rs201567166, ExAC 0.02%) but has not been reported in the literature in individuals with a RANBP2-related disease. This sequence change replaces phenylalanine with leucine at codon 1194 of the RANBP2 protein (p.Phe1194Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at