2-108782708-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_006267.5(RANBP2):c.9215C>T(p.Ala3072Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000768 in 1,614,022 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RANBP2 | NM_006267.5 | c.9215C>T | p.Ala3072Val | missense_variant | 28/29 | ENST00000283195.11 | NP_006258.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RANBP2 | ENST00000283195.11 | c.9215C>T | p.Ala3072Val | missense_variant | 28/29 | 1 | NM_006267.5 | ENSP00000283195.6 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152138Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251478Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135916
GnomAD4 exome AF: 0.0000821 AC: 120AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000853 AC XY: 62AN XY: 727244
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152138Hom.: 1 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74304
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2023 | The c.9215C>T (p.A3072V) alteration is located in exon 28 (coding exon 28) of the RANBP2 gene. This alteration results from a C to T substitution at nucleotide position 9215, causing the alanine (A) at amino acid position 3072 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Familial acute necrotizing encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 02, 2021 | This sequence change replaces alanine with valine at codon 3072 of the RANBP2 protein (p.Ala3072Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs368398572, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with RANBP2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 04, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at