NM_001356.5(DDX3X):c.1127G>A (p.Arg376His) AND Intellectual disability, X-linked 102

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 6, 2015
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001093534.3

Allele description [Variation Report for NM_001356.5(DDX3X):c.1127G>A (p.Arg376His)]

NM_001356.5(DDX3X):c.1127G>A (p.Arg376His)

Gene:

DDX3X:DEAD-box helicase 3 X-linked [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.4

Genomic location:

Preferred name:

NM_001356.5(DDX3X):c.1127G>A (p.Arg376His)

HGVS:

NC_000023.11:g.41345281G>A
NG_012830.2:g.16884G>A
NM_001193416.3:c.1127G>A
NM_001193417.3:c.1079G>A
NM_001356.5:c.1127G>AMANE SELECT
NM_001363819.1:c.569G>A
NP_001180345.1:p.Arg376His
NP_001180346.1:p.Arg360His
NP_001347.3:p.Arg376His
NP_001350748.1:p.Arg190His
NC_000023.10:g.41204534G>A
NM_001356.4:c.1127G>A
NR_126093.1:n.2072G>A

Protein change:

R190H; ARG376HIS

Links:

OMIM: 300160.0007; dbSNP: rs2063908570

NCBI 1000 Genomes Browser:

rs2063908570

Molecular consequence:

NM_001193416.3:c.1127G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001193417.3:c.1079G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001356.5:c.1127G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363819.1:c.569G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_126093.1:n.2072G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Intellectual disability, X-linked 102 (MRXSSB)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, SNIJDERS BLOK TYPE
Identifiers:: MONDO: MONDO:0010497; MedGen: C5393299; Orphanet: 457260; OMIM: 300958

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001250582	OMIM	no assertion criteria provided	Pathogenic (Aug 6, 2015)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 30734472, 26235985
SCV002098138	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001250582

OMIM

no assertion criteria provided

Pathogenic
(Aug 6, 2015)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV002098138

GeneReviews

no classification provided

not provided

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling.

Snijders Blok L, Madsen E, Juusola J, Gilissen C, Baralle D, Reijnders MR, Venselaar H, Helsmoortel C, Cho MT, Hoischen A, Vissers LE, Koemans TS, Wissink-Lindhout W, Eichler EE, Romano C, Van Esch H, Stumpel C, Vreeburg M, Smeets E, Oberndorff K, van Bon BW, Shaw M, et al.

Am J Hum Genet. 2015 Aug 6;97(2):343-52. doi: 10.1016/j.ajhg.2015.07.004. Epub 2015 Jul 30.

PubMed [citation]

PMID:: 26235985
PMCID:: PMC4573244

De novo DDX3X missense variants in males appear viable and contribute to syndromic intellectual disability.

Nicola P, Blackburn PR, Rasmussen KJ, Bertsch NL, Klee EW, Hasadsri L, Pichurin PN, Rankin J, Raymond FL; DDD Study., Clayton-Smith J.

Am J Med Genet A. 2019 Apr;179(4):570-578. doi: 10.1002/ajmg.a.61061. Epub 2019 Feb 7.

PubMed [citation]

PMID:: 30734472

Details of each submission

From OMIM, SCV001250582.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a 9-year-old boy (patient 1; Decipher ID: 301323) with Snijders Blok-type X-linked syndromic intellectual developmental disorder (MRXSSB; 300958), Nicola et al. (2019) identified a hemizygous c.1127G-A transition (c.1127G-A, NM_001356.4) in the DDX3X gene, resulting in an arg376-to-his (R376H) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was absent in the parents, suggesting a de novo mutation. A de novo mutation at the same codon (R376C; 300160.0001) was reported by Snijders Blok et al. (2015) in females with MRXSSB.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneReviews, SCV002098138.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

Observed in affected males w/de novo occurrence [Wang et al 2018, Nicola et al 2019]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 21, 2023

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