U.S. flag

An official website of the United States government

NM_000153.4(GALC):c.830G>A (p.Ser277Asn) AND Galactosylceramide beta-galactosidase deficiency

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Mar 8, 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:
RCV001250794.5

Allele description [Variation Report for NM_000153.4(GALC):c.830G>A (p.Ser277Asn)]

NM_000153.4(GALC):c.830G>A (p.Ser277Asn)

Gene:
GALC:galactosylceramidase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q31.3
Genomic location:
Preferred name:
NM_000153.4(GALC):c.830G>A (p.Ser277Asn)
HGVS:
  • NC_000014.9:g.87968413C>T
  • NG_011853.3:g.30151G>A
  • NM_000153.4:c.830G>AMANE SELECT
  • NM_001201401.2:c.761G>A
  • NM_001201402.2:c.752G>A
  • NP_000144.2:p.Ser277Asn
  • NP_001188330.1:p.Ser254Asn
  • NP_001188331.1:p.Ser251Asn
  • NC_000014.8:g.88434757C>T
  • NG_011853.2:g.30151G>A
  • NM_000153.3:c.830G>A
Protein change:
S251N
Links:
dbSNP: rs1886145312
NCBI 1000 Genomes Browser:
rs1886145312
Molecular consequence:
  • NM_000153.4:c.830G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001201401.2:c.761G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001201402.2:c.752G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Galactosylceramide beta-galactosidase deficiency
Synonyms:
Krabbe leukodystrophy; Globoid cell leukoencephalopathy; Galactocerebrosidase deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009499; MedGen: C0023521; Orphanet: 487; OMIM: 245200

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001244262Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jul 5, 2019)
inheritedresearch

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

SCV001250613Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,
no assertion criteria provided
Uncertain significanceinheritedclinical testing

SCV005040029Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Pathogenic
(Mar 8, 2024)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedinheritedyesnot providednot providednot providednot providednot providedclinical testing, research

Citations

PubMed

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

Genetic testing of leukodystrophies unraveling extensive heterogeneity in a large cohort and report of five common diseases and 38 novel variants.

Mahdieh N, Soveizi M, Tavasoli AR, Rabbani A, Ashrafi MR, Kohlschütter A, Rabbani B.

Sci Rep. 2021 Feb 5;11(1):3231. doi: 10.1038/s41598-021-82778-0.

PubMed [citation]
PMID:
33547378
PMCID:
PMC7864965
See all PubMed Citations (3)

Details of each submission

From Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, SCV001244262.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot providednot providednot providednot providednot provided

From Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,, SCV001250613.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005040029.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: GALC c.830G>A (p.Ser277Asn) results in a conservative amino acid change located in the Glycosyl hydrolase family 59, catalytic domain (IPR049161) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249284 control chromosomes. c.830G>A has been reported in the literature as a homozygous genotype in multiple individuals affected with features of Krabbe Disease/Leukodystrophies (example, Mahdieh_2021, Ashrafi_2023). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 37597066, 33547378). ClinVar contains an entry for this variant (Variation ID: 873006). Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Sep 16, 2024