X-77508409-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_000489.6(ATRX):c.7421G>A(p.Arg2474His) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,209,503 control chromosomes in the GnomAD database, including 1 homozygotes. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R2474R) has been classified as Likely benign.
Frequency
Consequence
NM_000489.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATRX | NM_000489.6 | c.7421G>A | p.Arg2474His | missense_variant | Exon 35 of 35 | ENST00000373344.11 | NP_000480.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000897 AC: 1AN: 111499Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33683
GnomAD3 exomes AF: 0.0000164 AC: 3AN: 183358Hom.: 0 AF XY: 0.0000295 AC XY: 2AN XY: 67832
GnomAD4 exome AF: 0.00000729 AC: 8AN: 1098004Hom.: 1 Cov.: 31 AF XY: 0.0000110 AC XY: 4AN XY: 363370
GnomAD4 genome AF: 0.00000897 AC: 1AN: 111499Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33683
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: ATRX c.7421G>A (p.Arg2474His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.4e-06 in 1209503 control chromosomes in the gnomAD database, including 1 homozygotes and 4 hemizygotes, a finding inconsistent with the early onset and severe nature of ATRX-related conditions. To our knowledge, no occurrence of c.7421G>A in individuals affected with ATR-X Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1636796). Based on the evidence outlined above, the variant was classified as likely benign. -
Alpha thalassemia-X-linked intellectual disability syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at