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NM_000829.4(GRIA4):c.1915A>T (p.Thr639Ser) AND Neurodevelopmental disorder with or without seizures and gait abnormalities

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 7, 2018
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:
RCV000578490.2

Allele description [Variation Report for NM_000829.4(GRIA4):c.1915A>T (p.Thr639Ser)]

NM_000829.4(GRIA4):c.1915A>T (p.Thr639Ser)

Gene:
GRIA4:glutamate ionotropic receptor AMPA type subunit 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000829.4(GRIA4):c.1915A>T (p.Thr639Ser)
HGVS:
  • NC_000011.10:g.105926808A>T
  • NM_000829.4:c.1915A>TMANE SELECT
  • NM_001077243.3:c.1915A>T
  • NP_000820.4:p.Thr639Ser
  • NP_001070711.3:p.Thr639Ser
  • NC_000011.9:g.105797534A>T
  • NM_000829.3:c.1915A>T
  • NR_046356.2:n.2207A>T
Protein change:
T639S; THR639SER
Links:
OMIM: 138246.0001; dbSNP: rs1555050158
NCBI 1000 Genomes Browser:
rs1555050158
Molecular consequence:
  • NM_000829.4:c.1915A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001077243.3:c.1915A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_046356.2:n.2207A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Neurodevelopmental disorder with or without seizures and gait abnormalities
Identifiers:
MONDO: MONDO:0060641; MedGen: C4693391; OMIM: 617864

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000680480OMIM
no assertion criteria provided
Pathogenic
(Feb 7, 2018) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

De Novo Variants in GRIA4 Lead to Intellectual Disability with or without Seizures and Gait Abnormalities.

Martin S, Chamberlin A, Shinde DN, Hempel M, Strom TM, Schreiber A, Johannsen J, Ousager LB, Larsen MJ, Hansen LK, Fatemi A, Cohen JS, Lemke J, Sørensen KP, Helbig KL, Lessel D, Abou Jamra R.

Am J Hum Genet. 2017 Dec 7;101(6):1013-1020. doi: 10.1016/j.ajhg.2017.11.004.

PubMed [citation]
PMID:
29220673
PMCID:
PMC5812909

Details of each submission

From OMIM, SCV000680480.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 15-year-old boy with neurodevelopmental disorder with seizures and gait abnormalities (NEDSGA; 617864), Martin et al. (2017) identified a de novo heterozygous c.1915A-T transversion (c.1915A-T, NM_000829.3) in the GRIA4 gene, resulting in a thr639-to-ser (T639S) substitution within the highly conserved SYTANLAAF motif near transmembrane 3. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed, but molecular modeling predicted that the mutation would alter gating properties of the channel with inhibition of channel closing allowing leakage or an open state, resulting in constitutive channel opening. The authors postulated a dominant functional effect rather than a loss of function.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 30, 2023