X-41333721-AC-A

Position:

• chrX-41333721-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.400

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]

ACMG classification

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	UniProt
DDX3X	XM_011543892.3	c.-531del		5_prime_UTR_variant	1/16
DDX3X	NR_126093.1	n.415del		non_coding_transcript_exon_variant	1/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX3X	ENST00000478993.5	c.-531del		5_prime_UTR_variant, NMD_transcript_variant	1/19	1
DDX3X	ENST00000625837.2	c.-531del		5_prime_UTR_variant	1/19	5
DDX3X	ENST00000626301.2	c.-531del		5_prime_UTR_variant	1/17	5

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1284 AN: 110698 Hom.: 27 Cov.: 22 AF XY: 0.00824 AC XY: 272 AN XY: 32996

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: 1 AN: 1364 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 460

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.: 27 Cov.: 22 AF XY: 0.00826 AC XY: 273 AN XY: 33046

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: 4 AN: 2521

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

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

Other links and lift over

dbSNP: rs145000030; hg19: chrX-41192974;