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NM_000487.6(ARSA):c.1195C>T (p.His399Tyr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Pathogenic(1);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Jul 30, 2020
Accession:
VCV000068117.3
Variation ID:
68117
Description:
single nucleotide variant
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NM_000487.6(ARSA):c.1195C>T (p.His399Tyr)

Allele ID
79008
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
22q13.33
Genomic location
22: 50625594 (GRCh38) GRCh38 UCSC
22: 51064022 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000022.10:g.51064022G>A
NC_000022.11:g.50625594G>A
NG_009260.2:g.7586C>T
... more HGVS
Protein change
H399Y, H313Y
Other names
-
Canonical SPDI
NC_000022.11:50625593:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA218990
UniProtKB/Swiss-Prot: VAR_007288
dbSNP: rs199476376
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jul 30, 2020 RCV000672049.3
not provided 1 no assertion provided - RCV000058947.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ARSA - - GRCh38
GRCh37
590 726

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jan 12, 2018)
criteria provided, single submitter
Method: clinical testing
Metachromatic leukodystrophy
Allele origin: unknown
Counsyl
Accession: SCV000797108.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (2)
Pathogenic
(Jul 30, 2020)
criteria provided, single submitter
Method: clinical testing
Metachromatic leukodystrophy
Allele origin: germline
Invitae
Accession: SCV001225560.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces histidine with tyrosine at codon 399 of the ARSA protein (p.His399Tyr). The histidine residue is highly conserved and there is a … (more)
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: not provided
UniProtKB/Swiss-Prot
Accession: SCV000090468.1
Submitted: (Apr 18, 2012)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Enzymatic characterization of novel arylsulfatase A variants using human arylsulfatase A-deficient immortalized mesenchymal stromal cells. Böhringer J Human mutation 2017 PMID: 28762252
Molecular bases of metachromatic leukodystrophy in Polish patients. Lugowska A Journal of human genetics 2010 PMID: 20339381
Metachromatic leukodystrophy: subtype genotype/phenotype correlations and identification of novel missense mutations (P148L and P191T) causing the juvenile-onset disease. Qu Y Molecular genetics and metabolism 1999 PMID: 10381328
Two novel mutations in the arylsulfatase A gene associated with juvenile (R390Q) and adult onset (H397Y) metachromatic leukodystrophy. Coulter-Mackie MB Human mutation 1998 PMID: 9452102

Text-mined citations for rs199476376...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 30, 2021