NM_000153.4(GALC):c.908C>T (p.Ser303Phe) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Aug 7, 2023
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:: RCV000522818.27

Allele description [Variation Report for NM_000153.4(GALC):c.908C>T (p.Ser303Phe)]

NM_000153.4(GALC):c.908C>T (p.Ser303Phe)

Gene:

GALC:galactosylceramidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q31.3

Genomic location:

Preferred name:

NM_000153.4(GALC):c.908C>T (p.Ser303Phe)

HGVS:

NC_000014.9:g.87968335G>A
NG_011853.3:g.30229C>T
NM_000153.4:c.908C>TMANE SELECT
NM_001201401.2:c.839C>T
NM_001201402.2:c.830C>T
NP_000144.2:p.Ser303Phe
NP_001188330.1:p.Ser280Phe
NP_001188331.1:p.Ser277Phe
NC_000014.8:g.88434679G>A
NG_011853.2:g.30229C>T
NM_000153.3:c.908C>T
P54803:p.Ser303Phe

Protein change:

S277F

Links:

UniProtKB: P54803#VAR_003392; dbSNP: rs756352952

NCBI 1000 Genomes Browser:

rs756352952

Molecular consequence:

NM_000153.4:c.908C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001201401.2:c.839C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001201402.2:c.830C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000330944	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Sep 29, 2015)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10448809, 20886637, 9338580 Citation Link,
SCV000617679	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Aug 7, 2023)	germline	clinical testing	Citation Link,
SCV001249967	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jan 1, 2017)	germline	clinical testing	Citation Link,
SCV002021213	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 4, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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	not provided	not provided	clinical testing
not provided	germline	unknown	5	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Protracted course of Krabbe disease in an adult patient bearing a novel mutation.

Jardim LB, Giugliani R, Pires RF, Haussen S, Burin MG, Rafi MA, Wenger DA.

Arch Neurol. 1999 Aug;56(8):1014-7.

PubMed [citation]

PMID:: 10448809

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

See all PubMed Citations (4)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000330944.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (3)

#	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		5	not provided	not provided	not provided

From GeneDx, SCV000617679.2

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

Description

Expression studies on COS-1 cells showed a dramatic reduction of GALC activity of the mutated expressed protein (Jardim et al., 1999); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 9338580, 20886637, 28598007, 33176815, 30089515, 11151421, 10448809)

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

From CeGaT Center for Human Genetics Tuebingen, SCV001249967.21

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

From Revvity Omics, Revvity, SCV002021213.3

#	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

Last Updated: May 12, 2024

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