rs1200376246
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000489.6(ATRX):c.5406A>G(p.Lys1802=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,789 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )
Consequence
ATRX
NM_000489.6 synonymous
NM_000489.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.07
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant X-77618848-T-C is Benign according to our data. Variant chrX-77618848-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 533645.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.07 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATRX | NM_000489.6 | c.5406A>G | p.Lys1802= | synonymous_variant | 21/35 | ENST00000373344.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATRX | ENST00000373344.11 | c.5406A>G | p.Lys1802= | synonymous_variant | 21/35 | 1 | NM_000489.6 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
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23
GnomAD3 exomes AF: 0.00000545 AC: 1AN: 183328Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67826
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GnomAD4 exome AF: 9.12e-7 AC: 1AN: 1096789Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 1AN XY: 362367
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GnomAD4 genome ? Cov.: 23
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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 | Invitae | Dec 30, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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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