rs1557140015
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_000489.6(ATRX):c.2262T>G(p.Ile754Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: not found (cov: 22)
Consequence
ATRX
NM_000489.6 missense
NM_000489.6 missense
Scores
4
12
Clinical Significance
Conservation
PhyloP100: 2.77
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 -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12914416).
BP6
Variant X-77682994-A-C is Benign according to our data. Variant chrX-77682994-A-C is described in ClinVar as [Benign]. Clinvar id is 533632.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ATRX | NM_000489.6 | c.2262T>G | p.Ile754Met | missense_variant | Exon 9 of 35 | ENST00000373344.11 | NP_000480.3 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
22
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
GnomAD4 genome
Cov.:
22
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Alpha thalassemia-X-linked intellectual disability syndrome Uncertain:1Benign:1
Feb 19, 2021
Natera, Inc.
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Mar 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;.;T;T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;.
REVEL
Benign
Sift
Uncertain
D;D;.;.
Sift4G
Benign
T;T;T;.
Polyphen
B;.;.;.
Vest4
MutPred
Gain of phosphorylation at T759 (P = 0.0866);.;.;.;
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at