NM_000155.4(GALT):c.1018G>A (p.Glu340Lys) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jun 12, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000022263.13

Allele description [Variation Report for NM_000155.4(GALT):c.1018G>A (p.Glu340Lys)]

NM_000155.4(GALT):c.1018G>A (p.Glu340Lys)

Gene:

GALT:galactose-1-phosphate uridylyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_000155.4(GALT):c.1018G>A (p.Glu340Lys)

HGVS:

NC_000009.12:g.34649523G>A
NG_009029.2:g.7935G>A
NG_028966.1:g.2339G>A
NM_000155.4:c.1018G>AMANE SELECT
NM_001258332.2:c.691G>A
NP_000146.2:p.Glu340Lys
NP_001245261.1:p.Glu231Lys
NC_000009.11:g.34649520G>A
NM_000155.3:c.1018G>A

Protein change:

E231K

Links:

dbSNP: rs111033806

NCBI 1000 Genomes Browser:

rs111033806

Molecular consequence:

NM_000155.4:c.1018G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258332.2:c.691G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase
Synonyms:: GALACTOSE-1-PHOSPHATE URIDYLYLTRANSFERASE DEFICIENCY; Galactose-1-phosphate uridyltransferase deficiency; Transferase Deficiency Galactosemia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009258; MedGen: C0268151; Orphanet: 352; Orphanet: 79239; OMIM: 230400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001377663	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 21, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10649501, 20213376, 22944367, 28065439, 28492532
SCV004198538	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 12, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001377663

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 21, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004198538

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 12, 2023)

unknown

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation analysis of the GALT gene in Czech and Slovak galactosemia populations: identification of six novel mutations, including a stop codon mutation (X380R).

Kozák L, Francová H, Fajkusová L, Pijácková A, Macku J, Stastná S, Peskovová K, Martincová O, Krijt J, Bzdúch V.

Hum Mutat. 2000 Feb;15(2):206.

PubMed [citation]

PMID:: 10649501

Molecular and clinical analysis of patients with classic and Duarte galactosemia in western Hungary.

Milánkovics I, Schuler A, Kámory E, Csókay B, Fodor F, Somogyi C, Németh K, Fekete G.

Wien Klin Wochenschr. 2010 Feb;122(3-4):95-102. doi: 10.1007/s00508-010-1311-7.

PubMed [citation]

PMID:: 20213376

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001377663.4

#	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 replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 340 of the GALT protein (p.Glu340Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GALT-related conditions (PMID: 10649501, 20213376, 22944367, 28065439). ClinVar contains an entry for this variant (Variation ID: 25317). 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 GALT protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Baylor Genetics, SCV004198538.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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