NM_000153.4(GALC):c.1153G>T (p.Glu385Ter) AND Galactosylceramide beta-galactosidase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 3, 2022
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:: RCV000004022.5

Allele description [Variation Report for NM_000153.4(GALC):c.1153G>T (p.Glu385Ter)]

NM_000153.4(GALC):c.1153G>T (p.Glu385Ter)

Gene:

GALC:galactosylceramidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q31.3

Genomic location:

Preferred name:

NM_000153.4(GALC):c.1153G>T (p.Glu385Ter)

HGVS:

NC_000014.9:g.87963392C>A
NG_011853.3:g.35172G>T
NM_000153.4:c.1153G>TMANE SELECT
NM_001201401.2:c.1084G>T
NM_001201402.2:c.1075G>T
NP_000144.2:p.Glu385Ter
NP_001188330.1:p.Glu362Ter
NP_001188331.1:p.Glu359Ter
NC_000014.8:g.88429736C>A
NG_011853.2:g.35172G>T

Protein change:

E359*; GLU385TER

Links:

OMIM: 606890.0001; dbSNP: rs121908010

NCBI 1000 Genomes Browser:

rs121908010

Molecular consequence:

NM_000153.4:c.1153G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001201401.2:c.1084G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001201402.2:c.1075G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000024188	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 2010)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8297359, 20886637
SCV003443440	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 7437911, 9272171, 16607461, 8297359, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000024188

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 2010)

germline

literature only

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

SCV003443440

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2022)

germline

clinical testing

PubMed (5)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.

Tappino B, Biancheri R, Mort M, Regis S, Corsolini F, Rossi A, Stroppiano M, Lualdi S, Fiumara A, Bembi B, Di Rocco M, Cooper DN, Filocamo M.

Hum Mutat. 2010 Dec;31(12):E1894-914. doi: 10.1002/humu.21367.

PubMed [citation]

PMID:: 20886637
PMCID:: PMC3052420

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

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000024188.2

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

Description

In a patient with typical Krabbe disease (KRB; 245200), Sakai et al. (1994) identified homozygosity for a GAA-to-TAA mutation in codon 385, predicting a glu385-to-ter (E385X) substitution. This mutation, originally reported as GLU369TER, has been renumbered based on the first ATG initiation codon as nucleotide +1 (Tappino et al., 2010).

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

From Invitae, SCV003443440.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Glu385*) 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 not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 3818). This variant is also known as codon 369 (GAA>TAA). This premature translational stop signal has been observed in individual(s) with Krabbe disease (PMID: 8297359).

#	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: Feb 14, 2024

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