rs1555953882
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001356.5(DDX3X):c.1276_1279delGACA(p.Asp426AsnfsTer9) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,851 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. D426D) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
DDX3X
NM_001356.5 frameshift
NM_001356.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.87
Publications
0 publications found
Genes affected
DDX3X (HGNC:2745): (DEAD-box helicase 3 X-linked) The protein encoded by this gene is a member of the large DEAD-box protein family, that is defined by the presence of the conserved Asp-Glu-Ala-Asp (DEAD) motif, and has ATP-dependent RNA helicase activity. This protein has been reported to display a high level of RNA-independent ATPase activity, and unlike most DEAD-box helicases, the ATPase activity is thought to be stimulated by both RNA and DNA. This protein has multiple conserved domains and is thought to play roles in both the nucleus and cytoplasm. Nuclear roles include transcriptional regulation, mRNP assembly, pre-mRNA splicing, and mRNA export. In the cytoplasm, this protein is thought to be involved in translation, cellular signaling, and viral replication. Misregulation of this gene has been implicated in tumorigenesis. This gene has a paralog located in the nonrecombining region of the Y chromosome. Pseudogenes sharing similarity to both this gene and the DDX3Y paralog are found on chromosome 4 and the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-41345506-TCAGA-T is Pathogenic according to our data. Variant chrX-41345506-TCAGA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 520543.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001356.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DDX3X | MANE Select | c.1276_1279delGACA | p.Asp426AsnfsTer9 | frameshift | Exon 12 of 17 | NP_001347.3 | |||
| DDX3X | c.1276_1279delGACA | p.Asp426AsnfsTer9 | frameshift | Exon 12 of 17 | NP_001180345.1 | A0A2R8YFS5 | |||
| DDX3X | c.1228_1231delGACA | p.Asp410AsnfsTer9 | frameshift | Exon 11 of 16 | NP_001180346.1 | O00571-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DDX3X | MANE Select | c.1276_1279delGACA | p.Asp426AsnfsTer9 | frameshift | Exon 12 of 17 | ENSP00000494040.1 | O00571-1 | ||
| DDX3X | TSL:1 | c.1273_1276delGACA | p.Asp425AsnfsTer9 | frameshift | Exon 12 of 17 | ENSP00000382840.3 | A0A2U3TZJ9 | ||
| DDX3X | TSL:1 | n.1276_1279delGACA | non_coding_transcript_exon | Exon 12 of 19 | ENSP00000478443.1 | O00571-1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
22
GnomAD4 exome AF: 9.13e-7 AC: 1AN: 1095851Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 361323 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1095851
Hom.:
AF XY:
AC XY:
0
AN XY:
361323
show subpopulations
African (AFR)
AF:
AC:
1
AN:
26302
American (AMR)
AF:
AC:
0
AN:
34758
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19309
East Asian (EAS)
AF:
AC:
0
AN:
30189
South Asian (SAS)
AF:
AC:
0
AN:
53495
European-Finnish (FIN)
AF:
AC:
0
AN:
40502
Middle Eastern (MID)
AF:
AC:
0
AN:
4114
European-Non Finnish (NFE)
AF:
AC:
0
AN:
841165
Other (OTH)
AF:
AC:
0
AN:
46017
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
22
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Inborn genetic diseases (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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