NM_000155.4(GALT):c.598del (p.Gln200fs) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Feb 5, 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:: RCV000022161.12

Allele description [Variation Report for NM_000155.4(GALT):c.598del (p.Gln200fs)]

NM_000155.4(GALT):c.598del (p.Gln200fs)

Gene:

GALT:galactose-1-phosphate uridylyltransferase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_000155.4(GALT):c.598del (p.Gln200fs)

HGVS:

NC_000009.12:g.34648367del
NG_009029.2:g.6779del
NG_028966.1:g.1183del
NM_000155.4:c.598delMANE SELECT
NM_001258332.2:c.271del
NP_000146.2:p.Gln200fs
NP_001245261.1:p.Gln91fs
NC_000009.11:g.34648362del
NC_000009.11:g.34648364del
NM_000155.2:c.598delC
NM_000155.4:c.598delCMANE SELECT

Protein change:

Q91fs

Links:

dbSNP: rs111033738

NCBI 1000 Genomes Browser:

rs111033738

Molecular consequence:

NM_000155.4:c.598del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258332.2:c.271del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Homo sapiens MIER1 transcriptional regulator (MIER1), transcript variant 1, mRNA
Homo sapiens MIER1 transcriptional regulator (MIER1), transcript variant 1, mRNA
gi|1677499184|ref|NM_020948.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000917423	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Dec 3, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11261429, 10408771 Citation Link,
SCV003440884	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22944367, 28391442, 28492532
SCV004198559	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 5, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000917423

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Dec 3, 2018)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV003440884

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 28, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004198559

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 5, 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

Citations

PubMed

The molecular biology of galactosemia.

Elsas LJ 2nd, Lai K.

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

PubMed [citation]

PMID:: 11261429

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 (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917423.1

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

Description

Variant summary: GALT c.598delC (p.Gln200SerfsX19) 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 (eg. c.610C>T (p.Arg204X) and c.947G>A (p.Trp316X)). The variant was absent in 246258 control chromosomes (gnomAD). c.598delC has been reported in the literature in an individual affected with Galactosemia (Tyfield_1999). These data do not allow any conclusion about variant significance. 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. Based on the evidence outlined above, the variant was classified as likely 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003440884.2

#	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 creates a premature translational stop signal (p.Gln200Serfs*19) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with classical galactosemia (PMID: 28391442). ClinVar contains an entry for this variant (Variation ID: 25225). 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 Baylor Genetics, SCV004198559.2

#	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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