NM_139058.3(ARX):c.856G>A (p.Gly286Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 27, 2023
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:: RCV001230602.11

Allele description [Variation Report for NM_139058.3(ARX):c.856G>A (p.Gly286Ser)]

NM_139058.3(ARX):c.856G>A (p.Gly286Ser)

Gene:

ARX:aristaless related homeobox [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.3

Genomic location:

Preferred name:

NM_139058.3(ARX):c.856G>A (p.Gly286Ser)

HGVS:

NC_000023.11:g.25013139C>T
NG_008281.1:g.7810G>A
NM_139058.3:c.856G>AMANE SELECT
NP_620689.1:p.Gly286Ser
NC_000023.10:g.25031256C>T
NM_139058.2:c.856G>A
Q96QS3:p.Gly286Ser

Protein change:

G286S; GLY286SER

Links:

UniProtKB: Q96QS3#VAR_015671; OMIM: 300382.0014; dbSNP: rs28935479

NCBI 1000 Genomes Browser:

rs28935479

Molecular consequence:

NM_139058.3:c.856G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 1 (DEE1)
Synonyms:: INFANTILE SPASM SYNDROME, X-LINKED 1; X-linked infantile spasms; West's syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010632; MedGen: C3463992; OMIM: 308350

Name:: Intellectual disability, X-linked, with or without seizures, arx-related (XLID29)
Synonyms:: MENTAL RETARDATION, X-LINKED 29; MENTAL RETARDATION, X-LINKED 32; MENTAL RETARDATION, X-LINKED 33; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010317; MedGen: C0796244; Orphanet: 777; OMIM: 300419

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001403086	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11971879, 30255221, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001403086

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 27, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation.

Bienvenu T, Poirier K, Friocourt G, Bahi N, Beaumont D, Fauchereau F, Ben Jeema L, Zemni R, Vinet MC, Francis F, Couvert P, Gomot M, Moraine C, van Bokhoven H, Kalscheuer V, Frints S, Gecz J, Ohzaki K, Chaabouni H, Fryns JP, Desportes V, Beldjord C, et al.

Hum Mol Genet. 2002 Apr 15;11(8):981-91.

PubMed [citation]

PMID:: 11971879

Mutations of ARX and non-syndromic intellectual disability in Chinese population.

Wu Y, Zhang H, Liu X, Shi Z, Li H, Wang Z, Jie X, Huang S, Zhang F, Li J, Zhang K, Gao X.

Genes Genomics. 2019 Jan;41(1):125-131. doi: 10.1007/s13258-018-0745-6. Epub 2018 Sep 25.

PubMed [citation]

PMID:: 30255221

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001403086.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 286 of the ARX protein (p.Gly286Ser). This variant is present in population databases (rs28935479, gnomAD 0.002%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with clinical features of ARX-related conditions (PMID: 11971879, 30255221; Invitae). ClinVar contains an entry for this variant (Variation ID: 11199). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ARX protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 20, 2024

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