Variant X-41334294-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP6_Moderate

The NM_001356.5(DDX3X):c.42G>C(p.Gln14His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 24)

Consequence

DDX3X
NM_001356.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.37

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DDX3X. . Gene score misZ: 4.3295 (greater than the threshold 3.09). The gene has 93 curated pathogenic missense variants (we use a threshold of 10). The gene has 20 curated benign missense variants. GenCC has associacion of the gene with X-linked intellectual disability-hypotonia-movement disorder syndrome, Toriello-Carey syndrome, intellectual disability, X-linked 102, X-linked syndromic intellectual disability.

BP6

Variant X-41334294-G-C is Benign according to our data. Variant chrX-41334294-G-C is described in ClinVar as [Benign]. Clinvar id is 1693000.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX3X	NM_001356.5 link	c.42G>C	p.Gln14His	missense_variant	1/17	ENST00000644876.2	NP_001347.3	O00571-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX3X	ENST00000644876.2 link	c.42G>C	p.Gln14His	missense_variant	1/17		NM_001356.5	ENSP00000494040.1		O00571-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, X-linked 102

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

D;D;.;T;.;.;.;.;.;.;.;.;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

.;.;D;D;D;.;D;D;D;D;D;D;D

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.50

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.7

M;M;.;.;M;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.4

.;.;.;.;N;.;D;.;.;.;.;D;.

REVEL

Benign

0.16

Sift

Uncertain

0.0040

.;.;.;.;D;.;.;.;.;.;.;D;.

Sift4G

Uncertain

0.0070

.;D;D;D;D;.;D;.;.;.;.;D;.

Polyphen

0.53

P;P;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.47, 0.46, 0.46, 0.55, 0.90, 0.47

MutPred

0.57

Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);Gain of catalytic residue at Q14 (P = 0.1199);

MVP

0.78

MPC

1.6

ClinPred

0.96

GERP RS

4.3

Varity_R

0.55

gMVP

0.74

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over