NM_000153.4(GALC):c.1507G>T (p.Glu503Ter) AND Galactosylceramide beta-galactosidase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 5, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003503482.2

Allele description [Variation Report for NM_000153.4(GALC):c.1507G>T (p.Glu503Ter)]

NM_000153.4(GALC):c.1507G>T (p.Glu503Ter)

Gene:

GALC:galactosylceramidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q31.3

Genomic location:

Preferred name:

NM_000153.4(GALC):c.1507G>T (p.Glu503Ter)

HGVS:

NC_000014.9:g.87945716C>A
NG_011853.3:g.52848G>T
NM_000153.4:c.1507G>TMANE SELECT
NM_001201401.2:c.1438G>T
NM_001201402.2:c.1429G>T
NM_001424071.1:c.1339G>T
NM_001424072.1:c.1339G>T
NM_001424073.1:c.1339G>T
NM_001424074.1:c.1159G>T
NM_001424075.1:c.1159G>T
NM_001424076.1:c.874G>T
NM_001424077.1:c.874G>T
NP_000144.2:p.Glu503Ter
NP_001188330.1:p.Glu480Ter
NP_001188331.1:p.Glu477Ter
NP_001411000.1:p.Glu447Ter
NP_001411001.1:p.Glu447Ter
NP_001411002.1:p.Glu447Ter
NP_001411003.1:p.Glu387Ter
NP_001411004.1:p.Glu387Ter
NP_001411005.1:p.Glu292Ter
NP_001411006.1:p.Glu292Ter
NC_000014.8:g.88412060C>A

Protein change:

E292*

Molecular consequence:

NM_000153.4:c.1507G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001201401.2:c.1438G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001201402.2:c.1429G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001424071.1:c.1339G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001424072.1:c.1339G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001424073.1:c.1339G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001424074.1:c.1159G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001424075.1:c.1159G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001424076.1:c.874G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001424077.1:c.874G>T - nonsense - [Sequence Ontology: SO:0001587]

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

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gi|291490950|gb|ADE06786.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004250138	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 5, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 7437911, 9272171, 16607461, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004250138

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 5, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

The Twitcher mouse: an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease).

Kobayashi T, Yamanaka T, Jacobs JM, Teixeira F, Suzuki K.

Brain Res. 1980 Dec 8;202(2):479-83.

PubMed [citation]

PMID:: 7437911

Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients.

Furuya H, Kukita Y, Nagano S, Sakai Y, Yamashita Y, Fukuyama H, Inatomi Y, Saito Y, Koike R, Tsuji S, Fukumaki Y, Hayashi K, Kobayashi T.

Hum Genet. 1997 Sep;100(3-4):450-6.

PubMed [citation]

PMID:: 9272171

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004250138.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Glu503*) in the GALC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with GALC-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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