rs953114

Positions:

• chrX-41338289-A-C
• chrX-41338289-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001356.5(DDX3X):​c.104-747A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (12703 hom., 17088 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: DDX3X NM_001356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX3X	NM_001356.5	c.104-747A>C		intron_variant		ENST00000644876.2	NP_001347.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX3X	ENST00000644876.2	c.104-747A>C		intron_variant			NM_001356.5	ENSP00000494040	A1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 59501 AN: 109402 Hom.: 12707 Cov.: 22 AF XY: 0.537 AC XY: 17042 AN XY: 31728

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.552

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.544 AC: 59541 AN: 109450 Hom.: 12703 Cov.: 22 AF XY: 0.538 AC XY: 17088 AN XY: 31786

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.559

Alfa AF: 0.442 Hom.: 41905

Bravo AF: 0.576

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs953114; hg19: chrX-41197542;