rs122445093
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_000489.6(ATRX):c.4826A>G(p.His1609Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1609Y) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000489.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATRX | NM_000489.6 | c.4826A>G | p.His1609Arg | missense_variant | 18/35 | ENST00000373344.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATRX | ENST00000373344.11 | c.4826A>G | p.His1609Arg | missense_variant | 18/35 | 1 | NM_000489.6 | P3 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
Alpha thalassemia-X-linked intellectual disability syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 24, 1995 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 22, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with ATRX-related disorder in published literature (Mitson et al., 2011); This variant is associated with the following publications: (PMID: 7697714, 21505078, 18409179) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at