rs121912421
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001111.5(ADAR):c.1420C>T(p.Arg474*) variant causes a stop gained 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R474R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001111.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAR | NM_001111.5 | c.1420C>T | p.Arg474* | stop_gained | 2/15 | ENST00000368474.9 | NP_001102.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAR | ENST00000368474.9 | c.1420C>T | p.Arg474* | stop_gained | 2/15 | 1 | NM_001111.5 | ENSP00000357459.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251456Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135902
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461890Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727246
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Symmetrical dyschromatosis of extremities;C3539013:Aicardi-Goutieres syndrome 6 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 23, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 14817). This premature translational stop signal has been observed in individual(s) with dyschromatosis symmetrica hereditaria (PMID: 12916015, 29915444). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121912421, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg474*) in the ADAR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADAR are known to be pathogenic (PMID: 22974014). - |
Symmetrical dyschromatosis of extremities Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2003 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at