rs761708272
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001111.5(ADAR):c.1402G>T(p.Ala468Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A468T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001111.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAR | NM_001111.5 | c.1402G>T | p.Ala468Ser | missense_variant | 2/15 | ENST00000368474.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAR | ENST00000368474.9 | c.1402G>T | p.Ala468Ser | missense_variant | 2/15 | 1 | NM_001111.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461890Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727246
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Aicardi-Goutieres syndrome 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Symmetrical dyschromatosis of extremities;C3539013:Aicardi-Goutieres syndrome 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2021 | 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine 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: 292778). This variant has not been reported in the literature in individuals affected with ADAR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 468 of the ADAR protein (p.Ala468Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. - |
Symmetrical dyschromatosis of extremities Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at