NM_001356.5(DDX3X):c.1486G>A (p.Val496Met) AND Intellectual disability, X-linked 102

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Jan 29, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000660645.8

Allele description [Variation Report for NM_001356.5(DDX3X):c.1486G>A (p.Val496Met)]

NM_001356.5(DDX3X):c.1486G>A (p.Val496Met)

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.1486G>A (p.Val496Met)

HGVS:

NC_000023.11:g.41346399G>A
NG_012830.2:g.18002G>A
NM_001193416.3:c.1486G>A
NM_001193417.3:c.1438G>A
NM_001356.5:c.1486G>AMANE SELECT
NM_001363819.1:c.928G>A
NP_001180345.1:p.Val496Met
NP_001180346.1:p.Val480Met
NP_001347.3:p.Val496Met
NP_001347.3:p.Val496Met
NP_001350748.1:p.Val310Met
NC_000023.10:g.41205652G>A
NM_001356.4:c.1486G>A
NR_126093.1:n.2431G>A

Protein change:

V310M; VAL496MET

Links:

OMIM: 300160.0008; dbSNP: rs1555954154

NCBI 1000 Genomes Browser:

rs1555954154

Molecular consequence:

NM_001193416.3:c.1486G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001193417.3:c.1438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001356.5:c.1486G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363819.1:c.928G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_126093.1:n.2431G>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
SCV000782770	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 29, 2018)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001250583	OMIM	no assertion criteria provided	Pathogenic (May 7, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002098139	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

SCV000782770

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 29, 2018)

de novo

clinical testing

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

SCV001250583

OMIM

no assertion criteria provided

Pathogenic
(May 7, 2020)

germline

literature only

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

SCV002098139

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	de novo	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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 Mayo Clinic Laboratories, Mayo Clinic, SCV000782770.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

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

From OMIM, SCV001250583.1

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

Description

In an 8-year-old boy (patient 2) with Snijders Blok-type X-linked syndromic intellectual developmental disorder (MRXSSB; 300958), Nicola et al. (2019) identified a de novo hemizygous c.1486G-A transition (c.1486G-A, NM_001356.4) in the DDX3X gene, resulting in a val496-to-met (V496M) substitution at a highly conserved reside in the helicase C-terminal domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database. The patient had impaired intellectual development, cardiac defects, cataracts, and mild conductive hearing loss.

#	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, SCV002098139.2

#	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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