NM_032436.4(CHAMP1):c.1192C>T (p.Arg398Ter) AND Intellectual disability, autosomal dominant 40

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 3, 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:: RCV000192002.5

Allele description [Variation Report for NM_032436.4(CHAMP1):c.1192C>T (p.Arg398Ter)]

NM_032436.4(CHAMP1):c.1192C>T (p.Arg398Ter)

Gene:

CHAMP1:chromosome alignment maintaining phosphoprotein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q34

Genomic location:

Preferred name:

NM_032436.4(CHAMP1):c.1192C>T (p.Arg398Ter)

HGVS:

NC_000013.11:g.114325034C>T
NG_051829.1:g.15700C>T
NM_001164144.3:c.1192C>T
NM_001164145.3:c.1192C>T
NM_032436.4:c.1192C>TMANE SELECT
NP_001157616.1:p.Arg398Ter
NP_001157617.1:p.Arg398Ter
NP_115812.1:p.Arg398Ter
NC_000013.10:g.115090509C>T
NM_001164144.1:c.1192C>T
NM_032436.2:c.1192C>T

Protein change:

R398*; ARG398TER

Links:

OMIM: 616327.0005; dbSNP: rs797044962

NCBI 1000 Genomes Browser:

rs797044962

Molecular consequence:

NM_001164144.3:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001164145.3:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_032436.4:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Intellectual disability, autosomal dominant 40 (NEDHILD)
Synonyms:: NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED LANGUAGE, AND DYSMORPHIC FEATURES
Identifiers:: MONDO: MONDO:0014699; MedGen: C5676894; OMIM: 616579

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000246269	OMIM	no assertion criteria provided	Pathogenic (Sep 3, 2015)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 26340335, 23020937
SCV002104231	GenomeConnect - Brain Gene Registry	no classification provided	not provided	de novo	phenotyping only

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000246269

OMIM

no assertion criteria provided

Pathogenic
(Sep 3, 2015)

germline

literature only

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

SCV002104231

GenomeConnect - Brain Gene Registry

no classification provided

not provided

de novo

phenotyping only

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	phenotyping only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment.

Hempel M, Cremer K, Ockeloen CW, Lichtenbelt KD, Herkert JC, Denecke J, Haack TB, Zink AM, Becker J, Wohlleber E, Johannsen J, Alhaddad B, Pfundt R, Fuchs S, Wieczorek D, Strom TM, van Gassen KL, Kleefstra T, Kubisch C, Engels H, Lessel D.

Am J Hum Genet. 2015 Sep 3;97(3):493-500. doi: 10.1016/j.ajhg.2015.08.003.

PubMed [citation]

PMID:: 26340335
PMCID:: PMC4564986

Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.

Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, Albrecht B, Bartholdi D, Beygo J, Di Donato N, Dufke A, Cremer K, Hempel M, Horn D, Hoyer J, Joset P, Röpke A, Moog U, Riess A, Thiel CT, Tzschach A, Wiesener A, et al.

Lancet. 2012 Nov 10;380(9854):1674-82. doi: 10.1016/S0140-6736(12)61480-9. Epub 2012 Sep 27.

PubMed [citation]

PMID:: 23020937

Details of each submission

From OMIM, SCV000246269.3

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

Description

In an 18-year-old boy (family C) of Dutch descent with neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features (NEDHILD; 616579), Hempel et al. (2015) identified a de novo heterozygous c.1192C-T transition in the CHAMP1 gene, resulting in an arg398-to-ter (R398X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 136), 1000 Genomes Project, or ExAC databases. Functional studies of the variant were not performed, but the mutation was predicted to result in a truncated protein lacking the functionally important C terminal domain. Hempel et al. (2015) noted that the same de novo R398X mutation was identified by Rauch et al. (2012) in 1 of 51 individuals with severe intellectual disability who underwent trio exome-sequencing. This patient (family E) had a similar phenotype as patient C.

#	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 GenomeConnect - Brain Gene Registry, SCV002104231.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	phenotyping only	not provided

Description

Variant interpreted as Pathogenic and reported on 04/01/2019 by lab or GTR ID 61756. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator John Constantino MD PhD from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.

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

Last Updated: Jun 9, 2024

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