rs375794120
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2
The NM_000489.6(ATRX):c.546A>T(p.Gln182His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,097,514 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q182Q) has been classified as Likely benign.
Frequency
Consequence
NM_000489.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATRX | NM_000489.6 | c.546A>T | p.Gln182His | missense_variant | 7/35 | ENST00000373344.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATRX | ENST00000373344.11 | c.546A>T | p.Gln182His | missense_variant | 7/35 | 1 | NM_000489.6 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome AF: 0.00000364 AC: 4AN: 1097514Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 362936
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Alpha thalassemia-X-linked intellectual disability syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2020 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ATRX-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 182 of the ATRX protein (p.Gln182His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at