rs148015780
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000373344.11(ATRX):c.846C>T(p.Ser282=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,209,247 control chromosomes in the GnomAD database, including 4 homozygotes. There are 517 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 0.0010 ( 1 hom., 26 hem., cov: 23)
Exomes 𝑓: 0.0014 ( 3 hom. 491 hem. )
Consequence
ATRX
ENST00000373344.11 synonymous
ENST00000373344.11 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.980
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=-0.82).
BP6
Variant X-77684410-G-A is Benign according to our data. Variant chrX-77684410-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 210501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-77684410-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.98 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00103 (115/111979) while in subpopulation NFE AF= 0.00175 (93/53154). AF 95% confidence interval is 0.00146. There are 1 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 26 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATRX | NM_000489.6 | c.846C>T | p.Ser282= | synonymous_variant | 9/35 | ENST00000373344.11 | NP_000480.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATRX | ENST00000373344.11 | c.846C>T | p.Ser282= | synonymous_variant | 9/35 | 1 | NM_000489.6 | ENSP00000362441 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00103 AC: 115AN: 111927Hom.: 1 Cov.: 23 AF XY: 0.000761 AC XY: 26AN XY: 34169
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GnomAD3 exomes AF: 0.000808 AC: 148AN: 183206Hom.: 1 AF XY: 0.000900 AC XY: 61AN XY: 67760
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GnomAD4 exome AF: 0.00142 AC: 1558AN: 1097268Hom.: 3 Cov.: 32 AF XY: 0.00135 AC XY: 491AN XY: 362662
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GnomAD4 genome AF: 0.00103 AC: 115AN: 111979Hom.: 1 Cov.: 23 AF XY: 0.000760 AC XY: 26AN XY: 34231
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 19, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 30, 2015 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 09, 2017 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Alpha thalassemia-X-linked intellectual disability syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
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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