dbSNP rs953114: DDX3X:n.1018A>C (chrX-41338289-A-C) – ACMG Classification: Likely_benign (-4 pts)

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.424

Publications

5 publications found

Variant links:

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

DDX3X links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX3X	NM_001356.5 link	c.104-747A>C		intron_variant	Intron 2 of 16	ENST00000644876.2	NP_001347.3	O00571-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX3X	ENST00000644876.2 link	c.104-747A>C		intron_variant	Intron 2 of 16		NM_001356.5	ENSP00000494040.1		O00571-1

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

59501

AN:

109402

Hom.:

12707

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.544

AC:

59541

AN:

109450

Hom.:

12703

Cov.:

AF XY:

0.538

AC XY:

17088

AN XY:

31786

show subpopulations

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:

AN:

209

European-Non Finnish (NFE)

AF:

0.408

AC:

21440

AN:

52516

Other (OTH)

AF:

0.559

AC:

829

AN:

1483

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

860

1720

2579

3439

4299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.462

Hom.:

56285

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

(source)

DANN

Benign

0.88

PhyloP100

-0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over