Variant X-41334492-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001356.5(DDX3X):c.45+195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 1,095,773 control chromosomes in the GnomAD database, including 3,371 homozygotes. There are 30,983 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 232 hom., 2187 hem., cov: 25)

Exomes 𝑓: 0.093 ( 3139 hom. 28796 hem. )

Consequence

DDX3X
NM_001356.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0220

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant X-41334492-C-T is Benign according to our data. Variant chrX-41334492-C-T is described in ClinVar as [Benign]. Clinvar id is 1272632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX3X	NM_001356.5 linkuse as main transcript	c.45+195C>T		intron_variant		ENST00000644876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX3X	ENST00000644876.2 linkuse as main transcript	c.45+195C>T		intron_variant			NM_001356.5	A1	O00571-1

Frequencies

GnomAD3 genomes

AF:

0.0662

AC:

7487

AN:

113102

Hom.:

230

Cov.:

AF XY:

0.0620

AC XY:

2185

AN XY:

35230

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.0519

Gnomad AMR

AF:

0.0685

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.0581

Gnomad FIN

AF:

0.0753

Gnomad MID

AF:

0.0753

Gnomad NFE

AF:

0.0864

Gnomad OTH

AF:

0.0900

GnomAD4 exome

AF:

0.0929

AC:

91268

AN:

982617

Hom.:

3139

Cov.:

AF XY:

0.0932

AC XY:

28796

AN XY:

309121

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.0475

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.0610

Gnomad4 FIN exome

AF:

0.0864

Gnomad4 NFE exome

AF:

0.0953

Gnomad4 OTH exome

AF:

0.0935

GnomAD4 genome

AF:

0.0662

AC:

7490

AN:

113156

Hom.:

232

Cov.:

AF XY:

0.0620

AC XY:

2187

AN XY:

35294

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.0686

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.0601

Gnomad4 FIN

AF:

0.0753

Gnomad4 NFE

AF:

0.0864

Gnomad4 OTH

AF:

0.0896

Alfa

AF:

0.0629

Hom.:

393

Bravo

AF:

0.0666

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.3

DANN

Benign

0.90

RBP_binding_hub_radar

0.77

RBP_regulation_power_radar

2.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over