rs782180867
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_000489.6(ATRX):āc.2859A>Gā(p.Thr953Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,209,977 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000018 ( 0 hom., 0 hem., cov: 22)
Exomes š: 0.000013 ( 0 hom. 3 hem. )
Consequence
ATRX
NM_000489.6 synonymous
NM_000489.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.975
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
Variant X-77682397-T-C is Benign according to our data. Variant chrX-77682397-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 465050.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.975 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000128 (14/1098021) while in subpopulation EAS AF= 0.000397 (12/30198). AF 95% confidence interval is 0.000229. There are 0 homozygotes in gnomad4_exome. There are 3 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Hemizygotes in GnomAdExome4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATRX | NM_000489.6 | c.2859A>G | p.Thr953Thr | 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.2859A>G | p.Thr953Thr | synonymous_variant | 9/35 | 1 | NM_000489.6 | ENSP00000362441.4 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111901Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34099
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GnomAD3 exomes AF: 0.0000547 AC: 10AN: 182967Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67643
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GnomAD4 exome AF: 0.0000128 AC: 14AN: 1098021Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 3AN XY: 363445
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GnomAD4 genome AF: 0.0000179 AC: 2AN: 111956Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34164
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Alpha thalassemia-X-linked intellectual disability syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at