rs398123423
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000489.6(ATRX):c.4374_4379del(p.Glu1463_Glu1464del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,204,437 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 21)
Exomes 𝑓: 0.0000046 ( 0 hom. 3 hem. )
Consequence
ATRX
NM_000489.6 inframe_deletion
NM_000489.6 inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.70
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 -4 ACMG points.
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.4374_4379del | p.Glu1463_Glu1464del | inframe_deletion | 15/35 | ENST00000373344.11 | NP_000480.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATRX | ENST00000373344.11 | c.4374_4379del | p.Glu1463_Glu1464del | inframe_deletion | 15/35 | 1 | NM_000489.6 | ENSP00000362441 | P3 | |
ATRX | ENST00000395603.7 | c.4260_4265del | p.Glu1425_Glu1426del | inframe_deletion | 14/34 | 1 | ENSP00000378967 | A2 | ||
ATRX | ENST00000480283.5 | c.*4002_*4007del | 3_prime_UTR_variant, NMD_transcript_variant | 16/36 | 1 | ENSP00000480196 | ||||
ATRX | ENST00000623242.3 | upstream_gene_variant | 3 | ENSP00000485183 |
Frequencies
GnomAD3 genomes AF: 0.00000909 AC: 1AN: 110027Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 32397
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GnomAD3 exomes AF: 0.0000168 AC: 3AN: 178979Hom.: 0 AF XY: 0.0000308 AC XY: 2AN XY: 65011
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GnomAD4 exome AF: 0.00000457 AC: 5AN: 1094410Hom.: 0 AF XY: 0.00000832 AC XY: 3AN XY: 360526
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GnomAD4 genome AF: 0.00000909 AC: 1AN: 110027Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 32397
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at