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NM_000487.6(ARSA):c.905G>T (p.Cys302Phe) AND Metachromatic leukodystrophy, late infantile form

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 20, 2003
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:
RCV000003239.3

Allele description [Variation Report for NM_000487.6(ARSA):c.905G>T (p.Cys302Phe)]

NM_000487.6(ARSA):c.905G>T (p.Cys302Phe)

Gene:
ARSA:arylsulfatase A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q13.33
Genomic location:
Preferred name:
NM_000487.6(ARSA):c.905G>T (p.Cys302Phe)
Other names:
C300F
HGVS:
  • NC_000022.11:g.50626228C>A
  • NG_009260.2:g.6952G>T
  • NM_000487.6:c.905G>TMANE SELECT
  • NM_001085425.3:c.905G>T
  • NM_001085426.3:c.905G>T
  • NM_001085427.3:c.905G>T
  • NM_001085428.3:c.647G>T
  • NM_001362782.2:c.647G>T
  • NP_000478.3:p.Cys302Phe
  • NP_001078894.2:p.Cys302Phe
  • NP_001078895.2:p.Cys302Phe
  • NP_001078896.2:p.Cys302Phe
  • NP_001078897.1:p.Cys216Phe
  • NP_001349711.1:p.Cys216Phe
  • NC_000022.10:g.51064656C>A
  • NM_000487.5:c.905G>T
Protein change:
C216F; CYS300PHE
Links:
UniProtKB/Swiss-Prot: VAR_008132; OMIM: 607574.0046; dbSNP: rs74315484
NCBI 1000 Genomes Browser:
rs74315484
Molecular consequence:
  • NM_000487.6:c.905G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085425.3:c.905G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085426.3:c.905G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085427.3:c.905G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085428.3:c.647G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362782.2:c.647G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Metachromatic leukodystrophy, late infantile form
Synonyms:
Metachromatic leukodystrophy, late infantile
Identifiers:
MONDO: MONDO:0017729; MedGen: C0751278

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000023397OMIM
no assertion criteria provided
Pathogenic
(Jun 20, 2003) 		germlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

Metachromatic leucodystrophy in Portugal-finding of four new molecular lesions: C300F, P425T, g.1190-1191insC, and g.2408delC. Mutations in brief no. 232. Online.

Marcão A, Amaral O, Pinto E, Pinto R, Sá Miranda MC.

Hum Mutat. 1999;13(4):337-8.

PubMed [citation]
PMID:
10220151

Biochemical characterization of two (C300F, P425T) arylsulfatase a missense mutations.

Marcão A, Simonis H, Schestag F, Sá Miranda MC, Gieselmann V.

Am J Med Genet A. 2003 Jan 30;116A(3):238-42.

PubMed [citation]
PMID:
12503099
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000023397.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In a Portuguese patient with severe late infantile MLD (250100), Marcao et al. (1999, 2003) identified a homozygous missense mutation in the ARSA gene, resulting in a cys300-to-phe (C300F) substitution. Transfection experiments with C300F cDNA demonstrated a reduction of ARSA enzyme activity to less than 1% of wildtype, and resulted in more rapid enzyme degradation in lysosomes. Using sedimentation analysis of the mutated protein, Marcao et al. (2003) showed that the C300F mutation strongly interfered with the octamerization process of ARSA at low pH, which may be related to the reduced lysosomal half-life of the enzyme.

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

Last Updated: Apr 23, 2022