rs186005081

Variant names:

• chrX-41333711-G-A
• rs186005081
• ENST00000478993.5:n.-542G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-41333711-G-A
• chrX-41333711-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000478993.5(DDX3X):​n.-542G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000488 in 102,551 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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 0.000049 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: DDX3X ENST00000478993.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• 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]

DDX3X Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 102

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

  Inheritance: XL Classification: DEFINITIVE Submitted by: Illumina, ClinGen
• 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

ENSG00000301689 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000478993.5. 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	NR_126093.1		n.404G>A		non_coding_transcript_exon	Exon 1 of 19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX3X	ENST00000478993.5	TSL:1	n.-542G>A		non_coding_transcript_exon	Exon 1 of 19	ENSP00000478443.1	O00571-1
	DDX3X	ENST00000478993.5	TSL:1	n.-542G>A		5_prime_UTR	Exon 1 of 19	ENSP00000478443.1	O00571-1
	DDX3X	ENST00000625837.2	TSL:5	c.-542G>A		5_prime_UTR	Exon 1 of 19	ENSP00000486306.1	A0A0D9SF53

Frequencies

GnomAD3 genomes AF: 0.0000488 AC: 5 AN: 102551 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 990 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 428

African (AFR) AF: 0.00 AC: 0 AN: 11

American (AMR) AF: 0.00 AC: 0 AN: 26

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7

East Asian (EAS) AF: 0.00 AC: 0 AN: 15

South Asian (SAS) AF: 0.00 AC: 0 AN: 275

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 193

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 427

Other (OTH) AF: 0.00 AC: 0 AN: 34

GnomAD4 genome AF: 0.0000488 AC: 5 AN: 102551 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 28019

African (AFR) AF: 0.000107 AC: 3 AN: 27941

American (AMR) AF: 0.000105 AC: 1 AN: 9544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2524

East Asian (EAS) AF: 0.00 AC: 0 AN: 3276

South Asian (SAS) AF: 0.00 AC: 0 AN: 2399

European-Finnish (FIN) AF: 0.000216 AC: 1 AN: 4635

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 223

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50024

Other (OTH) AF: 0.00 AC: 0 AN: 1354

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		-1.6
PromoterAI		-0.029	Neutral

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: rs186005081; hg19: chrX-41192964; COSMIC: COSV107511309;