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NM_000153.4(GALC):c.1591C>T (p.Arg531Cys)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Apr 7, 2021)
Last evaluated:
Mar 31, 2021
Accession:
VCV000188997.5
Variation ID:
188997
Description:
single nucleotide variant
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NM_000153.4(GALC):c.1591C>T (p.Arg531Cys)

Allele ID
186916
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q31.3
Genomic location
14: 87945632 (GRCh38) GRCh38 UCSC
14: 88411976 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000014.8:g.88411976G>A
NM_000153.4:c.1591C>T MANE Select NP_000144.2:p.Arg531Cys missense
P54803:p.Arg531Cys
... more HGVS
Protein change
R531C, R505C, R508C
Other names
-
Canonical SPDI
NC_000014.9:87945631:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00003
Exome Aggregation Consortium (ExAC) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00004
Links
ClinGen: CA274231
UniProtKB: P54803#VAR_003399
dbSNP: rs749893889
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 3 criteria provided, multiple submitters, no conflicts Mar 31, 2021 RCV000169377.4
Pathogenic 1 criteria provided, single submitter Jan 7, 2015 RCV001269916.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GALC - - GRCh38
GRCh37
701 722

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Oct 01, 2014)
criteria provided, single submitter
Method: literature only
Galactosylceramide beta-galactosidase deficiency
(Autosomal recessive inheritance)
Allele origin: unknown
Counsyl
Accession: SCV000220761.1
Submitted: (Mar 11, 2015)
Evidence details
Publications
PubMed (5)
Pathogenic
(Jan 07, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital
Accession: SCV001450274.1
Submitted: (Nov 26, 2020)
Evidence details
Pathogenic
(Mar 31, 2021)
criteria provided, single submitter
Method: clinical testing
Galactosylceramide beta-galactosidase deficiency
(Autosomal recessive inheritance)
Allele origin: germline
Centre for Inherited Metabolic Diseases, Karolinska University Hospital
Accession: SCV001554469.1
Submitted: (Apr 07, 2021)
Evidence details
Likely pathogenic
(Oct 19, 2020)
criteria provided, single submitter
Method: clinical testing
Galactosylceramide beta-galactosidase deficiency
Allele origin: germline
Invitae
Accession: SCV001234986.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (9)
Comment:
This sequence change replaces arginine with cysteine at codon 531 of the GALC protein (p.Arg531Cys). The arginine residue is highly conserved and there is a … (more)

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
Early progression of Krabbe disease in patients with symptom onset between 0 and 5 months. Beltran-Quintero ML Orphanet journal of rare diseases 2019 PMID: 30777126
Whole exome sequencing as a diagnostic adjunct to clinical testing in fetuses with structural abnormalities. Fu F Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 2018 PMID: 28976722
Expression of individual mutations and haplotypes in the galactocerebrosidase gene identified by the newborn screening program in New York State and in confirmed cases of Krabbe's disease. Saavedra-Matiz CA Journal of neuroscience research 2016 PMID: 27638593
Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants. Spratley SJ Traffic (Copenhagen, Denmark) 2016 PMID: 27126738
Newborn screening for Krabbe disease in New York State: the first eight years' experience. Orsini JJ Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26795590
Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a review. Debs R Journal of inherited metabolic disease 2013 PMID: 23197103
Later onset phenotypes of Krabbe disease: results of the world-wide registry. Duffner PK Pediatric neurology 2012 PMID: 22520351
Insights into Krabbe disease from structures of galactocerebrosidase. Deane JE Proceedings of the National Academy of Sciences of the United States of America 2011 PMID: 21876145
Early infantile Krabbe disease: results of the World-Wide Krabbe Registry. Duffner PK Pediatric neurology 2011 PMID: 21824559
The earliest MR imaging and proton MR spectroscopy abnormalities in adult-onset Krabbe disease. Wang C Acta neurologica Scandinavica 2007 PMID: 17824908
Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation. Xu C Journal of human genetics 2006 PMID: 16607461
Molecular heterogeneity of Krabbe disease. Fu L Journal of inherited metabolic disease 1999 PMID: 10234611
Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications. Wenger DA Human mutation 1997 PMID: 9338580

Text-mined citations for rs749893889...

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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 24, 2021