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NM_000487.6(ARSA):c.931G>A (p.Gly311Ser)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Pathogenic(3);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
9 (Most recent: Nov 19, 2021)
Last evaluated:
Dec 21, 2019
Accession:
VCV000003060.20
Variation ID:
3060
Description:
single nucleotide variant
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NM_000487.6(ARSA):c.931G>A (p.Gly311Ser)

Allele ID
18099
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
22q13.33
Genomic location
22: 50626202 (GRCh38) GRCh38 UCSC
22: 51064630 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000022.11:g.50626202C>T
NG_009260.2:g.6978G>A
NM_000487.6:c.931G>A MANE Select NP_000478.3:p.Gly311Ser missense
... more HGVS
Protein change
G311S, G225S
Other names
ARSA, GLY309SER
Canonical SPDI
NC_000022.11:50626201:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
Links
ClinGen: CA115967
OMIM: 607574.0011
dbSNP: rs74315459
VarSome
Comment on variant
NCBI staff reviewed the sequence information reported in PubMed 8101038 to determine the location of this allele on current reference sequence (G311S).
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Aug 7, 2018 RCV000714802.2
Conflicting interpretations of pathogenicity 7 criteria provided, conflicting interpretations Dec 21, 2019 RCV000666302.10
Pathogenic 1 no assertion criteria provided Aug 1, 1993 RCV000003206.2
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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
593 729

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Apr 04, 2017)
criteria provided, single submitter
Method: clinical testing
Metachromatic leukodystrophy
Allele origin: unknown
Counsyl
Accession: SCV000790571.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (5)
Uncertain significance
(Aug 07, 2018)
criteria provided, single submitter
Method: clinical testing
Pseudoarylsulfatase A deficiency
Allele origin: inherited
Genomic Research Center,Shahid Beheshti University of Medical Sciences
Accession: SCV000845536.1
Submitted: (Aug 07, 2018)
Evidence details
Uncertain significance
(Jan 01, 2019)
criteria provided, single submitter
Method: clinical testing
Metachromatic leukodystrophy
Allele origin: inherited
Genomic Research Center,Shahid Beheshti University of Medical Sciences
Accession: SCV000923448.1
Submitted: (Apr 08, 2019)
Evidence details
Pathogenic
(May 13, 2019)
criteria provided, single submitter
Method: clinical testing
Metachromatic leukodystrophy
Allele origin: germline
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001429286.1
Submitted: (Apr 20, 2020)
Evidence details
Comment:
This variant was identified as homozygous
Pathogenic
(Dec 21, 2019)
criteria provided, single submitter
Method: clinical testing
Metachromatic leukodystrophy
Allele origin: germline
Invitae
Accession: SCV001198547.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces glycine with serine at codon 311 of the ARSA protein (p.Gly311Ser). The glycine residue is highly conserved and there is a … (more)
Pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
Metachromatic leukodystrophy
(Autosomal recessive inheritance)
Allele origin: inherited
Kasturba Medical College, Manipal, Manipal Academy of Higher Education
Accession: SCV001963619.1
Submitted: (Oct 04, 2021)
Evidence details
Pathogenic
(Aug 01, 1993)
no assertion criteria provided
Method: literature only
METACHROMATIC LEUKODYSTROPHY, LATE INFANTILE
Allele origin: germline
OMIM
Accession: SCV000023364.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
Metachromatic leukodystrophy
(Autosomal recessive inheritance)
Allele origin: inherited
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,
Accession: SCV001426665.1
Submitted: (Sep 01, 2020)
Evidence details
Likely pathogenic
(Jan 16, 2020)
no assertion criteria provided
Method: clinical testing
Metachromatic leukodystrophy
Allele origin: germline
PerkinElmer Genomics
Accession: SCV002021438.1
Submitted: (Nov 19, 2021)
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
Four novel <i>ARSA</i> gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations. Dehghan Manshadi M Therapeutics and clinical risk management 2017 PMID: 28670130
Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy. Cesani M Human mutation 2016 PMID: 26462614
Sixteen novel mutations in the arylsulfatase A gene causing metachromatic leukodystrophy. Luzi P Gene 2013 PMID: 24001781
Missense mutations as a cause of metachromatic leukodystrophy. Degradation of arylsulfatase A in the endoplasmic reticulum. Poeppel P The FEBS journal 2005 PMID: 15720392
Novel mutations associated with metachromatic leukodystrophy: phenotype and expression studies in nine Czech and Slovak patients. Berná L American journal of medical genetics. Part A 2004 PMID: 15326627
High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy. Kreysing J American journal of human genetics 1993 PMID: 8101038

Text-mined citations for rs74315459...

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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 Nov 28, 2021