chrX-77683789-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000489.6(ATRX):c.1467C>T(p.Thr489=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,207,535 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 108 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., 7 hem., cov: 23)
Exomes 𝑓: 0.00028 ( 0 hom. 101 hem. )
Consequence
ATRX
NM_000489.6 synonymous
NM_000489.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0330
Genes affected
ATRX (HGNC:886): (ATRX chromatin remodeler) The protein encoded by this gene contains an ATPase/helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. This protein is found to undergo cell cycle-dependent phosphorylation, which regulates its nuclear matrix and chromatin association, and suggests its involvement in the gene regulation at interphase and chromosomal segregation in mitosis. Mutations in this gene are associated with X-linked syndromes exhibiting cognitive disabilities as well as alpha-thalassemia (ATRX) syndrome. These mutations have been shown to cause diverse changes in the pattern of DNA methylation, which may provide a link between chromatin remodeling, DNA methylation, and gene expression in developmental processes. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant X-77683789-G-A is Benign according to our data. Variant chrX-77683789-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 434462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.033 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000206 (23/111679) while in subpopulation SAS AF= 0.00037 (1/2701). AF 95% confidence interval is 0.000144. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 7 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATRX | NM_000489.6 | c.1467C>T | p.Thr489= | synonymous_variant | 9/35 | ENST00000373344.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATRX | ENST00000373344.11 | c.1467C>T | p.Thr489= | synonymous_variant | 9/35 | 1 | NM_000489.6 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000206 AC: 23AN: 111624Hom.: 0 Cov.: 23 AF XY: 0.000207 AC XY: 7AN XY: 33864
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GnomAD3 exomes AF: 0.000312 AC: 57AN: 182887Hom.: 0 AF XY: 0.000355 AC XY: 24AN XY: 67561
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GnomAD4 exome AF: 0.000276 AC: 303AN: 1095856Hom.: 0 Cov.: 32 AF XY: 0.000280 AC XY: 101AN XY: 361336
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GnomAD4 genome AF: 0.000206 AC: 23AN: 111679Hom.: 0 Cov.: 23 AF XY: 0.000206 AC XY: 7AN XY: 33929
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | ATRX: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 18, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 03, 2016 | - - |
Alpha thalassemia-X-linked intellectual disability syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
ATRX-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at