NM_000153.4(GALC):c.1589T>C (p.Leu530Pro) AND Galactosylceramide beta-galactosidase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 22, 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:: RCV002250959.1

Allele description [Variation Report for NM_000153.4(GALC):c.1589T>C (p.Leu530Pro)]

NM_000153.4(GALC):c.1589T>C (p.Leu530Pro)

Gene:

GALC:galactosylceramidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q31.3

Genomic location:

Preferred name:

NM_000153.4(GALC):c.1589T>C (p.Leu530Pro)

HGVS:

NC_000014.9:g.87945634A>G
NG_011853.3:g.52930T>C
NM_000153.4:c.1589T>CMANE SELECT
NM_001201401.2:c.1520T>C
NM_001201402.2:c.1511T>C
NP_000144.2:p.Leu530Pro
NP_001188330.1:p.Leu507Pro
NP_001188331.1:p.Leu504Pro
NC_000014.8:g.88411978A>G

Protein change:

L504P

Links:

dbSNP: rs2139951392

NCBI 1000 Genomes Browser:

rs2139951392

Molecular consequence:

NM_000153.4:c.1589T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001201401.2:c.1520T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001201402.2:c.1511T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV002521217	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28598007, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521217

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 22, 2022)

germline

clinical testing

PubMed (2)
[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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Large-scale study of clinical and biochemical characteristics of Chinese patients diagnosed with Krabbe disease.

Zhao S, Zhan X, Wang Y, Ye J, Han L, Qiu W, Gao X, Gu X, Zhang H.

Clin Genet. 2018 Feb;93(2):248-254. doi: 10.1111/cge.13071. Epub 2017 Oct 17.

PubMed [citation]

PMID:: 28598007

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 3billion, SCV002521217.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.88; 3Cnet: 0.57). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with GALC related disorder (PMID: 28598007). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline.

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

Last Updated: Dec 24, 2023

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