rs796052235
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_001356.5(DDX3X):c.1463G>A(p.Arg488His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R488C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001356.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDX3X | NM_001356.5 | c.1463G>A | p.Arg488His | missense_variant | 13/17 | ENST00000644876.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDX3X | ENST00000644876.2 | c.1463G>A | p.Arg488His | missense_variant | 13/17 | NM_001356.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 488 of the DDX3X protein (p.Arg488His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of DDX3X-related conditions (PMID: 26235985, 33504798). In at least one individual the variant was observed to be de novo. This variant is also known as X:41205629G>A. ClinVar contains an entry for this variant (Variation ID: 207817). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts the p.Arg488 amino acid residue in DDX3X. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30734472, 32135084, 33504798). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2021 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function This variant is associated with the following publications: (PMID: 26235985) - |
Intellectual disability, X-linked 102 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | May 17, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at