NM_000155.4(GALT):c.610C>T (p.Arg204Ter) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Feb 1, 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:: RCV000022164.21

Allele description [Variation Report for NM_000155.4(GALT):c.610C>T (p.Arg204Ter)]

NM_000155.4(GALT):c.610C>T (p.Arg204Ter)

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.610C>T (p.Arg204Ter)

HGVS:

NC_000009.12:g.34648379C>T
NG_009029.2:g.6791C>T
NG_028966.1:g.1195C>T
NM_000155.4:c.610C>TMANE SELECT
NM_001258332.2:c.283C>T
NP_000146.2:p.Arg204Ter
NP_001245261.1:p.Arg95Ter
NC_000009.11:g.34648376C>T
NG_009029.1:g.6742C>T
NM_000155.1:c.610C>T
NM_000155.3:c.610C>T
NP_000146.2:p.Arg204*
p.Arg204X

Protein change:

R204*

Links:

dbSNP: rs111033737

NCBI 1000 Genomes Browser:

rs111033737

Molecular consequence:

NM_000155.4:c.610C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001258332.2:c.283C>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

Clear Turn Off Turn On

Homo sapiens PR domain-containing protein 1 alpha (PRDM1) mRNA, complete cds
Homo sapiens PR domain-containing protein 1 alpha (PRDM1) mRNA, complete cds
gi|28630980|gb|AY198414.1|

Nucleotide
PREDICTED: Homo sapiens PR/SET domain 1 (PRDM1), transcript variant X1, mRNA
PREDICTED: Homo sapiens PR/SET domain 1 (PRDM1), transcript variant X1, mRNA
gi|2217362765|ref|XM_011536062.4|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000052470	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Aug 20, 2020)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 11754113, 10408771, 19224951, 10649501, 11216901, 17041746, 18210213, 19375122, 12595586 Citation Link,
SCV000220666	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Sep 3, 2014)	unknown	literature only	PubMed (10) [See all records that cite these PMIDs] 22944367, 20213376, 19375122, 17041746, 10408771, 10649501, 12595586, 19224951, 18210213, 11754113 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV000818515	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 30, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 12595586, 17041746, 18210213, 19224951, 19375122, 20213376, 22944367, 28492532
SCV004198512	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 1, 2024)	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, literature only

Citations

PubMed

Galactosaemia and allelic variation at the galactose-1-phosphate uridyltransferase gene: a complex relationship between genotype and phenotype.

Tyfield LA.

Eur J Pediatr. 2000 Dec;159 Suppl 3:S204-7. Review.

PubMed [citation]

PMID:: 11216901

Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene.

Tyfield L, Reichardt J, Fridovich-Keil J, Croke DT, Elsas LJ 2nd, Strobl W, Kozak L, Coskun T, Novelli G, Okano Y, Zekanowski C, Shin Y, Boleda MD.

Hum Mutat. 1999;13(6):417-30. Review.

PubMed [citation]

PMID:: 10408771

See all PubMed Citations (13)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000052470.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

Variant summary: GALT c.610C>T (p.Arg204X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 251502 control chromosomes (gnomAD and publication data). c.610C>T has been reported in the literature in multiple individuals affected with Galactosemia (Tyfield_1999, Webb_2003, Gort_2006, Chhay_2008, Carney_2009). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal GLAT activity (Chhay_2008). One ClinVar submitter (evaluation after 2014) cites 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 Counsyl, SCV000220666.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (10)

#	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 Invitae, SCV000818515.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

ClinVar contains an entry for this variant (Variation ID: 25228). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Arg204*) 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). This variant is present in population databases (rs111033737, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with galactosemia (PMID: 12595586, 17041746, 18210213, 19224951, 19375122, 20213376, 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 Baylor Genetics, SCV004198512.2

#	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: Jun 17, 2024

ClinVar

Relating variation to medicine