NM_000155.4(GALT):c.983G>A (p.Arg328His) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Nov 26, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000022254.5

Allele description [Variation Report for NM_000155.4(GALT):c.983G>A (p.Arg328His)]

NM_000155.4(GALT):c.983G>A (p.Arg328His)

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.983G>A (p.Arg328His)
HGVS:
  • NC_000009.12:g.34649488G>A
  • NG_009029.2:g.7900G>A
  • NG_028966.1:g.2304G>A
  • NM_000155.4:c.983G>AMANE SELECT
  • NM_001258332.2:c.656G>A
  • NP_000146.2:p.Arg328His
  • NP_001245261.1:p.Arg219His
  • NC_000009.11:g.34649485G>A
  • NM_000155.2:c.983G>A
  • P07902:p.Arg328His
Protein change:
R219H
Links:
UniProtKB: P07902#VAR_002622; dbSNP: rs111033802
NCBI 1000 Genomes Browser:
rs111033802
Molecular consequence:
  • NM_000155.4:c.983G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258332.2:c.656G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase (GALAC1)
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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000919406Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Nov 26, 2018)
germlineclinical testing

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

Citation Link,

SCV001163251Baylor Geneticscriteria provided, single submitter
Pathogenicgermlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Analysis of galactosemia-linked mutations of GALT enzyme using a computational biology approach.

Facchiano A, Marabotti A.

Protein Eng Des Sel. 2010 Feb;23(2):103-13. doi: 10.1093/protein/gzp076. Epub 2009 Dec 11.

PubMed [citation]
PMID:
20008339

The molecular biology of galactosemia.

Elsas LJ 2nd, Lai K.

Genet Med. 1998 Nov-Dec;1(1):40-8. Review.

PubMed [citation]
PMID:
11261429
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919406.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: GALT c.983G>A (p.Arg328His) results in a non-conservative amino acid change located in the Galactose-1-phosphate uridyl transferase, C-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function, including one computational study that considers the Arg328 H-bond with Arg-51 essential for protein function (Facchiano_2009). The variant allele was found at a frequency of 4.1e-06 in 246246 control chromosomes (gnomAD). The variant, c.983G>A, has been reported in the literature in individuals affected with Galactosemia, including a homozygote (Ozgul_2013, Elsas_1998). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, with one lab calling it pathogenic in 2012. A different variant affecting the same codon, c.982C>T (p.Arg328Cys), was classified as likely pathogenic internally, suggesting this codon could play an important role in protein function. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV001163251.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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