X-41338289-A-C

Variant names:

• chrX-41338289-A-C
• rs953114
• ENST00000480592.6:n.1018A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000480592.6(DDX3X):​n.1018A>C variant causes a non coding transcript exon 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 ENST00000480592.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 5 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]

DDX3X Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 102

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• Toriello-Carey syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked intellectual disability-hypotonia-movement disorder syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000480592.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX3X	NM_001356.5	MANE Select	c.104-747A>C		intron	N/A	NP_001347.3
	DDX3X	NR_126094.2		n.793A>C		non_coding_transcript_exon	Exon 3 of 3
	DDX3X	NM_001363819.1		c.-1202A>C		5_prime_UTR	Exon 3 of 17	NP_001350748.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX3X	ENST00000480592.6	TSL:1	n.1018A>C		non_coding_transcript_exon	Exon 2 of 2
	DDX3X	ENST00000644876.2	MANE Select	c.104-747A>C		intron	N/A	ENSP00000494040.1
	DDX3X	ENST00000399959.7	TSL:1	c.104-750A>C		intron	N/A	ENSP00000382840.3

Frequencies

GnomAD3 genomes AF: 0.544 AC: 59501 AN: 109402 Hom.: 12707 Cov.: 22

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 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

African (AFR) AF: 0.721 AC: 21648 AN: 30026

American (AMR) AF: 0.632 AC: 6494 AN: 10273

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1148 AN: 2603

East Asian (EAS) AF: 0.961 AC: 3363 AN: 3499

South Asian (SAS) AF: 0.732 AC: 1833 AN: 2503

European-Finnish (FIN) AF: 0.408 AC: 2312 AN: 5666

Middle Eastern (MID) AF: 0.459 AC: 96 AN: 209

European-Non Finnish (NFE) AF: 0.408 AC: 21440 AN: 52516

Other (OTH) AF: 0.559 AC: 829 AN: 1483

Alfa AF: 0.462 Hom.: 56285

Bravo AF: 0.576

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.88
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs953114; hg19: chrX-41197542;