Variant X-41333721-AC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000478993.5(DDX3X):c.-531del variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 110,738 control chromosomes in the GnomAD database, including 27 homozygotes. There are 273 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 27 hom., 273 hem., cov: 22)

Exomes 𝑓: 0.00073 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

DDX3X
ENST00000478993.5 5_prime_UTR, NMD_transcript

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.400

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 -10 ACMG points.

BP6

Variant X-41333721-AC-A is Benign according to our data. Variant chrX-41333721-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1213607.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1284/110738) while in subpopulation AFR AF= 0.0394 (1196/30384). AF 95% confidence interval is 0.0375. There are 27 homozygotes in gnomad4. There are 273 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX3X	XM_011543892.3 linkuse as main transcript	c.-531del		5_prime_UTR_variant	1/16		XP_011542194.1
DDX3X	NR_126093.1 linkuse as main transcript	n.415del		non_coding_transcript_exon_variant	1/19

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
DDX3X	ENST00000478993.5 linkuse as main transcript	c.-531del	5_prime_UTR_variant, NMD_transcript_variant	1/19	1	ENSP00000478443	O00571-1
DDX3X	ENST00000625837.2 linkuse as main transcript	c.-531del	5_prime_UTR_variant	1/19	5	ENSP00000486306
DDX3X	ENST00000626301.2 linkuse as main transcript	c.-531del	5_prime_UTR_variant	1/17	5	ENSP00000486443

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1284

AN:

110698

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

272

AN XY:

32996

show subpopulations

Gnomad AFR

AF:

0.0394

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00670

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000946

Gnomad OTH

AF:

0.00864

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000733

AC:

AN:

1364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

460

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0139

GnomAD4 genome

AF:

0.0116

AC:

1284

AN:

110738

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

273

AN XY:

33046

show subpopulations

Gnomad4 AFR

AF:

0.0394

Gnomad4 AMR

AF:

0.00670

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000946

Gnomad4 OTH

AF:

0.00854

Asia WGS

AF:

0.00159

AC:

AN:

2521

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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