NM_000155.4(GALT):c.820+13A>G AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Germline classification:: Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:: Feb 16, 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:: RCV000022211.18

Allele description [Variation Report for NM_000155.4(GALT):c.820+13A>G]

NM_000155.4(GALT):c.820+13A>G

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.820+13A>G

HGVS:

NC_000009.12:g.34648907A>G
NG_009029.2:g.7319A>G
NG_028966.1:g.1723A>G
NM_000155.4:c.820+13A>GMANE SELECT
NM_001258332.2:c.493+13A>G
NC_000009.11:g.34648904A>G
NM_000155.3:c.820+13A>G

Links:

dbSNP: rs111033768

NCBI 1000 Genomes Browser:

rs111033768

Molecular consequence:

NM_000155.4:c.820+13A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001258332.2:c.493+13A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase
Synonyms:: GALACTOSE-1-PHOSPHATE URIDYLYLTRANSFERASE DEFICIENCY; Transferase Deficiency Galactosemia; GALACTOSEMIA I; 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
SCV000486157	Counsyl	no assertion criteria provided	Likely pathogenic (Apr 7, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25052314, 23749220
SCV001137805	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001222162	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 16, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23749220, 25052314, 28492532
SCV002600456	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Oct 12, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15633893, 17041746, 10384398, 23749220, 33335841, 30994193 Citation Link,
SCV005058867	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 15, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005675424	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 19, 2024)	germline	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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional correction by antisense therapy of a splicing mutation in the GALT gene.

Coelho AI, Lourenço S, Trabuco M, Silva MJ, Oliveira A, Gaspar A, Diogo L, Tavares de Almeida I, Vicente JB, Rivera I.

Eur J Hum Genet. 2015 Apr;23(4):500-6. doi: 10.1038/ejhg.2014.149. Epub 2014 Jul 23.

PubMed [citation]

PMID:: 25052314
PMCID:: PMC4666580

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

See all PubMed Citations (9)

Details of each submission

From Counsyl, SCV000486157.2

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

#	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 Mendelics, SCV001137805.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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, SCV001222162.6

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

Description

This sequence change falls in intron 8 of the GALT gene. It does not directly change the encoded amino acid sequence of the GALT protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with galactosemia (PMID: 23749220, 25052314). ClinVar contains an entry for this variant (Variation ID: 25269). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002600456.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Variant summary: GALT c.820+13A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant strengthens a cryptic intronic 5' splicing donor site. One predicts the variant creates a cryptic intronic 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251064 control chromosomes. c.820+13A>G has been reported in the literature as compound heterozygous and homozygous genotype in multiple individuals affected with and in a carrier of classic Galactosemia (example, Gort_2006, Coelho_2014, Papachristoforou_2019, Crespo_2020). 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 (Coelho_2014, Crespo_2014). The most pronounced variant effect results in 0% of normal activity in a homozygous individual. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely 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, SCV005058867.1

#	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

From Fulgent Genetics, Fulgent Genetics, SCV005675424.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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