NM_000153.4(GALC):c.1006G>A (p.Val336Met) AND Galactosylceramide beta-galactosidase deficiency

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Jan 31, 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:: RCV000383198.16

Allele description [Variation Report for NM_000153.4(GALC):c.1006G>A (p.Val336Met)]

NM_000153.4(GALC):c.1006G>A (p.Val336Met)

Gene:

GALC:galactosylceramidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q31.3

Genomic location:

Preferred name:

NM_000153.4(GALC):c.1006G>A (p.Val336Met)

HGVS:

NC_000014.9:g.87965532C>T
NG_011853.3:g.33032G>A
NM_000153.4:c.1006G>AMANE SELECT
NM_001201401.2:c.937G>A
NM_001201402.2:c.928G>A
NP_000144.2:p.Val336Met
NP_001188330.1:p.Val313Met
NP_001188331.1:p.Val310Met
NC_000014.8:g.88431876C>T
NG_011853.2:g.33032G>A
NM_000153.3:c.1006G>A

Protein change:

V310M

Links:

dbSNP: rs185073540

NCBI 1000 Genomes Browser:

rs185073540

Molecular consequence:

NM_000153.4:c.1006G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001201401.2:c.937G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001201402.2:c.928G>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

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Rattus norvegicus strain BN chromosome 3 CRA_213000034348451, whole genome shotg...
Rattus norvegicus strain BN chromosome 3 CRA_213000034348451, whole genome shotgun sequence
gi|70583922|gb|AAHX01021929.1||gnl| AHX|CRA_213000034348451

Nucleotide
ORF073 [Staphylococcus phage 47]
ORF073 [Staphylococcus phage 47]
gi|66395712|ref|YP_240056.1|

Protein
Arabidopsis thaliana cytochrome P450, family 71, subfamily A, polypeptide 18 (CY...
Arabidopsis thaliana cytochrome P450, family 71, subfamily A, polypeptide 18 (CYP71A18), partial mRNA
gi|1063682622|ref|NM_101034.3|

Nucleotide
Eel River basin pequenovirus isolate c15438, complete genome
Eel River basin pequenovirus isolate c15438, complete genome
gi|755259306|gb|KP087947.1|

Nucleotide
chromosome 21 open reading frame 66, isoform CRA_d [Homo sapiens]
chromosome 21 open reading frame 66, isoform CRA_d [Homo sapiens]
gi|119630265|gb|EAX09860.1||gnl|WGS |hCP1729121

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000389250	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV000794543	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely benign (Sep 29, 2017)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26795590, 27638593 Citation Link,
SCV001014264	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002093638	Natera, Inc.	no assertion criteria provided	Likely benign (Apr 3, 2020)	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Newborn screening for Krabbe disease in New York State: the first eight years' experience.

Orsini JJ, Kay DM, Saavedra-Matiz CA, Wenger DA, Duffner PK, Erbe RW, Biski C, Martin M, Krein LM, Nichols M, Kurtzberg J, Escolar ML, Adams DJ, Arnold GL, Iglesias A, Galvin-Parton P, Kronn DF, Kwon JM, Levy PA, Pellegrino JE, Shur N, Wasserstein MP, et al.

Genet Med. 2016 Mar;18(3):239-48. doi: 10.1038/gim.2015.211. Epub 2016 Jan 21.

PubMed [citation]

PMID:: 26795590

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, Luzi P, Nichols M, Orsini JJ, Caggana M, Wenger DA.

J Neurosci Res. 2016 Nov;94(11):1076-83. doi: 10.1002/jnr.23905.

PubMed [citation]

PMID:: 27638593

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000389250.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000794543.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001014264.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002093638.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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