NM_000155.4(GALT):c.86A>G (p.His29Arg) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 26, 2021
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:: RCV001998181.6

Allele description [Variation Report for NM_000155.4(GALT):c.86A>G (p.His29Arg)]

NM_000155.4(GALT):c.86A>G (p.His29Arg)

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.86A>G (p.His29Arg)

HGVS:

NC_000009.12:g.34647092A>G
NG_009029.2:g.5504A>G
NM_000155.4:c.86A>GMANE SELECT
NM_001258332.2:c.-117A>G
NP_000146.2:p.His29Arg
NC_000009.11:g.34647089A>G

Protein change:

H29R

Links:

dbSNP: rs2132341442

NCBI 1000 Genomes Browser:

rs2132341442

Molecular consequence:

NM_001258332.2:c.-117A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000155.4:c.86A>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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aurora kinase A isoform 1 [Homo sapiens]
aurora kinase A isoform 1 [Homo sapiens]
gi|38327572|ref|NP_940839.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002257507	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 26, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30718057, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002257507

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 26, 2021)

germline

clinical testing

PubMed (2)
[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

Citations

PubMed

The ability of an LC-MS/MS-based erythrocyte GALT enzyme assay to predict the phenotype in subjects with GALT deficiency.

Demirbas D, Huang X, Daesety V, Feenstra S, Haskovic M, Qi W, Gubbels CS, Hecht L, Levy HL, Waisbren SE, Berry GT.

Mol Genet Metab. 2019 Apr;126(4):368-376. doi: 10.1016/j.ymgme.2019.01.016. Epub 2019 Jan 22.

PubMed [citation]

PMID:: 30718057

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002257507.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (ExAC no frequency). 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. 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. This missense change has been observed in individual(s) with GALT-related conditions (PMID: 30718057). This sequence change replaces histidine with arginine at codon 29 of the GALT protein (p.His29Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine.

#	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: Sep 29, 2024

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