NM_001008216.2(GALE):c.905G>A (p.Gly302Asp) AND UDPglucose-4-epimerase deficiency

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Oct 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:: RCV000020295.5

Allele description [Variation Report for NM_001008216.2(GALE):c.905G>A (p.Gly302Asp)]

NM_001008216.2(GALE):c.905G>A (p.Gly302Asp)

Gene:

GALE:UDP-galactose-4-epimerase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.11

Genomic location:

Preferred name:

NM_001008216.2(GALE):c.905G>A (p.Gly302Asp)

HGVS:

NC_000001.11:g.23796234C>T
NG_007068.1:g.9571G>A
NM_000403.4:c.905G>A
NM_001008216.2:c.905G>AMANE SELECT
NM_001127621.2:c.905G>A
NP_000394.2:p.Gly302Asp
NP_001008217.1:p.Gly302Asp
NP_001121093.1:p.Gly302Asp
NC_000001.10:g.24122724C>T
NM_000403.3:c.905G>A
NM_001008216.1:c.905G>A
Q14376:p.Gly302Asp

Protein change:

G302D

Links:

UniProtKB: Q14376#VAR_037739; dbSNP: rs137853861

NCBI 1000 Genomes Browser:

rs137853861

Molecular consequence:

NM_000403.4:c.905G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001008216.2:c.905G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127621.2:c.905G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: UDPglucose-4-epimerase deficiency
Synonyms:: GALACTOSEMIA III; Galactose epimerase deficiency; UDP-Galactose-4-epimerase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009257; MedGen: C0751161; Orphanet: 352; OMIM: 230350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000040660	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004276153	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 5, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16301867, 19250319, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000040660

GeneReviews

no classification provided

not provided

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV004276153

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 5, 2023)

germline

clinical testing

PubMed (3)
[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, literature only

Citations

PubMed

The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency galactosemia in Korean patients.

Park HD, Park KU, Kim JQ, Shin CH, Yang SW, Lee DH, Song YH, Song J.

Genet Med. 2005 Nov-Dec;7(9):646-9.

PubMed [citation]

PMID:: 16301867

Functional analysis of mutations in UDP-galactose-4-epimerase (GALE) associated with galactosemia in Korean patients using mammalian GALE-null cells.

Bang YL, Nguyen TT, Trinh TT, Kim YJ, Song J, Song YH.

FEBS J. 2009 Apr;276(7):1952-61. doi: 10.1111/j.1742-4658.2009.06922.x. Epub 2009 Feb 23.

PubMed [citation]

PMID:: 19250319

See all PubMed Citations (3)

Details of each submission

From GeneReviews, SCV000040660.3

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

Description

Account for 67% of alleles reported in a cohort of asymptomatic Koreans with peripheral epimerase deficiency galactosemia

#	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 Invitae, SCV004276153.1

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 302 of the GALE protein (p.Gly302Asp). This variant is present in population databases (rs137853861, gnomAD 0.02%). This missense change has been observed in individual(s) with galactose epimerase deficiency (PMID: 16301867). ClinVar contains an entry for this variant (Variation ID: 21173). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALE protein function. Experimental studies have shown that this missense change affects GALE function (PMID: 19250319). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: Feb 20, 2024

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