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NM_003900.5(SQSTM1):c.286C>T (p.Arg96Ter) AND Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset

Germline classification:
Pathogenic (3 submissions)
Last evaluated:
Mar 20, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000256198.3

Allele description [Variation Report for NM_003900.5(SQSTM1):c.286C>T (p.Arg96Ter)]

NM_003900.5(SQSTM1):c.286C>T (p.Arg96Ter)

Gene:
SQSTM1:sequestosome 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q35.3
Genomic location:
Preferred name:
NM_003900.5(SQSTM1):c.286C>T (p.Arg96Ter)
HGVS:
  • NC_000005.10:g.179823038C>T
  • NG_011342.1:g.21651C>T
  • NM_001142298.2:c.34C>T
  • NM_001142299.2:c.34C>T
  • NM_003900.5:c.286C>TMANE SELECT
  • NP_001135770.1:p.Arg12Ter
  • NP_001135771.1:p.Arg12Ter
  • NP_003891.1:p.Arg96Ter
  • NC_000005.9:g.179250038C>T
  • NM_003900.4:c.286C>T
Protein change:
R12*; ARG96TER
Links:
OMIM: 601530.0010; dbSNP: rs886039782
NCBI 1000 Genomes Browser:
rs886039782
Molecular consequence:
  • NM_001142298.2:c.34C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001142299.2:c.34C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003900.5:c.286C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
2

Condition(s)

Name:
Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset (NADGP)
Identifiers:
MONDO: MONDO:0014940; MedGen: C4310693; OMIM: 617145

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000322748OMIM
no assertion criteria provided
Pathogenic
(Oct 10, 2016)
germlineliterature only

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

SCV003804938Institute of Human Genetics, University Hospital Muenster
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jan 4, 2022)
unknownclinical testing

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

SCV004801680Centre for Inherited Metabolic Diseases, Karolinska University Hospital
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Mar 20, 2024)
inheritedclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedinheritedyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Absence of the Autophagy Adaptor SQSTM1/p62 Causes Childhood-Onset Neurodegeneration with Ataxia, Dystonia, and Gaze Palsy.

Haack TB, Ignatius E, Calvo-Garrido J, Iuso A, Isohanni P, Maffezzini C, Lönnqvist T, Suomalainen A, Gorza M, Kremer LS, Graf E, Hartig M, Berutti R, Paucar M, Svenningsson P, Stranneheim H, Brandberg G, Wedell A, Kurian MA, Hayflick SA, Venco P, Tiranti V, et al.

Am J Hum Genet. 2016 Sep 1;99(3):735-743. doi: 10.1016/j.ajhg.2016.06.026. Epub 2016 Aug 18.

PubMed [citation]
PMID:
27545679
PMCID:
PMC5010644

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

Details of each submission

From OMIM, SCV000322748.1

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

Description

In 2 sibs, born of consanguineous Kurdish parents, with childhood-onset neurodegeneration with ataxia, dystonia, and gaze palsy (NADGP; 617145), Haack et al. (2016) identified a homozygous c.286C-T transition (c.286C-T, NM_003900.4) in exon 2 of the SQSTM1 gene, resulting in an arg96-to-ter (R96X) substitution. An unrelated girl of Finnish descent was also homozygous for this mutation; her parents were not related. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing in both families, was filtered against the ExAC database, and segregated with the disorder in the families. Biallelic loss of function SQSTM1 mutations were not found in 7,000 in-house exomes or in the ExAC database. Patient fibroblasts showed absence of the SQSTM1 protein.

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

From Institute of Human Genetics, University Hospital Muenster, SCV003804938.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

ACMG categories: PVS1,PS1,PP5

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providedbloodnot provided1not providednot providednot provided

From Centre for Inherited Metabolic Diseases, Karolinska University Hospital, SCV004801680.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Mar 30, 2024