NM_000153.4(GALC):c.997G>A (p.Gly333Arg) AND Galactosylceramide beta-galactosidase deficiency

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(2);Uncertain significance(1) (Last evaluated: Dec 6, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000288663.6

Allele description [Variation Report for NM_000153.4(GALC):c.997G>A (p.Gly333Arg)]

NM_000153.4(GALC):c.997G>A (p.Gly333Arg)

Gene:
GALC:galactosylceramidase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q31.3
Genomic location:
Preferred name:
NM_000153.4(GALC):c.997G>A (p.Gly333Arg)
HGVS:
  • NC_000014.9:g.87965541C>T
  • NG_011853.2:g.33023G>A
  • NG_011853.3:g.33023G>A
  • NM_000153.4:c.997G>AMANE SELECT
  • NM_000153.4:c.997G>AMANE SELECT
  • NM_001201401.2:c.928G>A
  • NM_001201402.2:c.919G>A
  • NP_000144.2:p.Gly333Arg
  • NP_000144.2:p.Gly333Arg
  • NP_001188330.1:p.Gly310Arg
  • NP_001188331.1:p.Gly307Arg
  • NC_000014.8:g.88431885C>T
  • NC_000014.8:g.88431885C>T
  • NM_000153.3:c.997G>A
Protein change:
G307R
Links:
dbSNP: rs190921137
NCBI 1000 Genomes Browser:
rs190921137
Molecular consequence:
  • NM_000153.4:c.997G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001201401.2:c.928G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001201402.2:c.919G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000389251Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Likely benign
(Jan 13, 2018)
germlineclinical testing

Citation Link,

SCV001014769Invitaecriteria provided, single submitter
Likely benign
(Dec 6, 2020)
germlineclinical testing

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

SCV001461644Natera, Inc.no assertion criteria providedUncertain significance
(Apr 18, 2020)
germlineclinical testing

SCV001528222Baylor Geneticscriteria provided, single submitter
Uncertain significance
(Sep 27, 2018)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

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

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000389251.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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

From Invitae, SCV001014769.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Natera, Inc., SCV001461644.1

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

From Baylor Genetics, SCV001528222.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

Last Updated: Oct 24, 2021

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