NM_000155.4(GALT):c.598C>T (p.Gln200Ter) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jan 24, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000781404.3

Allele description [Variation Report for NM_000155.4(GALT):c.598C>T (p.Gln200Ter)]

NM_000155.4(GALT):c.598C>T (p.Gln200Ter)

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.598C>T (p.Gln200Ter)
HGVS:
  • NC_000009.12:g.34648367C>T
  • NG_009029.2:g.6779C>T
  • NG_028966.1:g.1183C>T
  • NM_000155.4:c.598C>TMANE SELECT
  • NM_001258332.2:c.271C>T
  • NP_000146.2:p.Gln200Ter
  • NP_001245261.1:p.Gln91Ter
  • NC_000009.11:g.34648364C>T
  • NM_000155.2:c.598C>T
  • NM_000155.3:c.598C>T
Protein change:
Q200*
Links:
dbSNP: rs1564101619
NCBI 1000 Genomes Browser:
rs1564101619
Molecular consequence:
  • NM_000155.4:c.598C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001258332.2:c.271C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase (GALAC1)
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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000919405Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Apr 24, 2018)
germlineclinical testing

Citation Link,

SCV001205862Invitaecriteria provided, single submitter
Pathogenic
(Jan 24, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919405.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: GALT c.598C>T (p.Gln200X) 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; c.947G>A, p.Trp316X). The variant was absent in 121398 control chromosomes. To our knowledge, no occurrence of c.598C>T in individuals affected with and no experimental evidence demonstrating its impact on protein function have 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001205862.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Gln200*) in the GALT gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GALT-related conditions. Loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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