NM_000155.4(GALT):c.634C>T (p.Gln212Ter) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Mar 20, 2024
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:: RCV000022170.18

Allele description [Variation Report for NM_000155.4(GALT):c.634C>T (p.Gln212Ter)]

NM_000155.4(GALT):c.634C>T (p.Gln212Ter)

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.634C>T (p.Gln212Ter)

HGVS:

NC_000009.12:g.34648403C>T
NG_009029.2:g.6815C>T
NG_028966.1:g.1219C>T
NM_000155.4:c.634C>TMANE SELECT
NM_001258332.2:c.307C>T
NP_000146.2:p.Gln212Ter
NP_001245261.1:p.Gln103Ter
NC_000009.11:g.34648400C>T
NM_000155.3:c.634C>T
NP_000146.2:p.Gln212*

Protein change:

Q103*

Links:

dbSNP: rs111033746

NCBI 1000 Genomes Browser:

rs111033746

Molecular consequence:

NM_000155.4:c.634C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258332.2:c.307C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

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BioProjects for Gene (Select 850660) (2)
BioProject
Conserved Domain Links for Gene (Select 850660) (2)
Conserved Domains
Y' element ATP-dependent helicase [Saccharomyces cerevisiae S288C]
Y' element ATP-dependent helicase [Saccharomyces cerevisiae S288C]
gi|6322962|ref|NP_013034.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000220970	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Dec 18, 2014)	unknown	literature only	PubMed (3) [See all records that cite these PMIDs] 8522334, 17876724, 9222760 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV002214759	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 22, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8522334, 22944367, 28492532
SCV002819759	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Dec 23, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15633893, 17876724, 8522334, 30172461 Citation Link,
SCV004198524	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 20, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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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, literature only

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

Mutation spectrum in the French cohort of galactosemic patients and structural simulation of 27 novel missense variations.

Boutron A, Marabotti A, Facchiano A, Cheillan D, Zater M, Oliveira C, Costa C, Labrune P, Brivet M; French Galactosemia Working Group..

Mol Genet Metab. 2012 Nov;107(3):438-47. doi: 10.1016/j.ymgme.2012.07.025. Epub 2012 Aug 6.

PubMed [citation]

PMID:: 22944367

See all PubMed Citations (8)

Details of each submission

From Counsyl, SCV000220970.2

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

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002214759.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with galactosemia (PMID: 8522334). ClinVar contains an entry for this variant (Variation ID: 25234). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln212*) in the GALT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367).

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002819759.1

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

Description

Variant summary: GALT c.634C>T (p.Gln212X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251472 control chromosomes (gnomAD). c.634C>T has been reported in the literature in compound heterozygous state in multiple individuals affected with Galactosemia (e.g. Gathof_1995, Yuzyuk_2018), where the complete lack of enzyme activity was noted in patient derived red blood cells. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was 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, SCV004198524.2

#	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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