NM_000155.4(GALT):c.367C>G (p.Arg123Gly) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 2, 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:: RCV000022078.10

Allele description [Variation Report for NM_000155.4(GALT):c.367C>G (p.Arg123Gly)]

NM_000155.4(GALT):c.367C>G (p.Arg123Gly)

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.367C>G (p.Arg123Gly)

HGVS:

NC_000009.12:g.34647695C>G
NG_009029.2:g.6107C>G
NG_028966.1:g.511C>G
NM_000155.4:c.367C>GMANE SELECT
NM_001258332.2:c.51-137C>G
NP_000146.2:p.Arg123Gly
NC_000009.11:g.34647692C>G
NM_000155.3:c.367C>G
P07902:p.Arg123Gly

Links:

UniProtKB: P07902#VAR_002565; dbSNP: rs111033674

NCBI 1000 Genomes Browser:

rs111033674

Molecular consequence:

NM_001258332.2:c.51-137C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000155.4:c.367C>G - 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
SCV000755881	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9222760, 31194682, 11397328, 28492532
SCV004198529	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 2, 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

SCV000755881

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004198529

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 2, 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

Molecular heterogeneity of classical and Duarte galactosemia: mutation analysis by denaturing gradient gel electrophoresis.

Greber-Platzer S, Guldberg P, Scheibenreiter S, Item C, Schuller E, Patel N, Strobl W.

Hum Mutat. 1997;10(1):49-57.

PubMed [citation]

PMID:: 9222760

Clinical and molecular characteristics and time of diagnosis of patients with classical galactosemia in an unscreened population in Turkey.

Teke Kisa P, Kose M, Unal O, Er E, Hismi BO, Bulbul FS, Kose E, Gunduz M, Canda E, Kucukcongar A, Arslan N.

J Pediatr Endocrinol Metab. 2019 Jul 26;32(7):675-681. doi: 10.1515/jpem-2018-0457.

PubMed [citation]

PMID:: 31194682

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000755881.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 123 of the GALT protein (p.Arg123Gly). This variant is present in population databases (rs111033674, gnomAD 0.01%). This missense change has been observed in individual(s) with galactosemia (PMID: 9222760, 31194682). ClinVar contains an entry for this variant (Variation ID: 25147). 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 with a positive predictive value of 95%. This variant disrupts the p.Arg123 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11397328). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as 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

From Baylor Genetics, SCV004198529.2

#	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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