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NM_139058.3(ARX):c.1449-1G>C AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 29, 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:
RCV003792884.2

Allele description [Variation Report for NM_139058.3(ARX):c.1449-1G>C]

NM_139058.3(ARX):c.1449-1G>C

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.1449-1G>C
HGVS:
  • NC_000023.11:g.25004911C>G
  • NG_008281.1:g.16038G>C
  • NG_146804.1:g.374C>G
  • NM_139058.3:c.1449-1G>CMANE SELECT
  • NC_000023.10:g.25023028C>G
Molecular consequence:
  • NM_139058.3:c.1449-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004578511Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 29, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splice variant in ARX leading to loss of C-terminal region in a boy with intellectual disability and infantile onset developmental and epileptic encephalopathy.

Shoubridge C, Jackson M, Grinton B, Berkovic SF, Scheffer IE, Huskins S, Thomas A, Ware T.

Am J Med Genet A. 2019 Aug;179(8):1483-1490. doi: 10.1002/ajmg.a.61216. Epub 2019 May 30.

PubMed [citation]
PMID:
31145546

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004578511.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 4 of the ARX gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with developmental and epileptic encephalopathy (PMID: 31145546). It has also been observed to segregate with disease in related individuals. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

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

Last Updated: Oct 8, 2024