NM_000155.3(GALT):c.790_792invCTA (p.Leu264Ter) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Clinical significance:Pathogenic (Last evaluated: Dec 19, 2020)

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:
RCV000555777.6

Allele description [Variation Report for NM_000155.3(GALT):c.790_792invCTA (p.Leu264Ter)]

NM_000155.3(GALT):c.790_792invCTA (p.Leu264Ter)

Gene:
GALT:galactose-1-phosphate uridylyltransferase [Gene - OMIM - HGNC]
Variant type:
Inversion
Cytogenetic location:
9p13.3
Genomic location:
Preferred name:
NM_000155.3(GALT):c.790_792invCTA (p.Leu264Ter)
HGVS:
  • NC_000009.12:g.34648864_34648866inv
  • NG_009029.2:g.7276_7278inv
  • NG_028966.1:g.1680_1682inv
  • NM_000155.4:c.790_792invMANE SELECT
  • NM_001258332.2:c.463_465inv
  • NP_000146.2:p.Leu264Ter
  • NP_001245261.1:p.Leu155Ter
  • M60091.1:c.[790delC;792_793insG]
  • NC_000009.11:g.34648861_34648863inv
  • NG_009029.1:g.7227_7229delCTAinsTAG
  • NM_000155.2:c.790_792delCTAinsTAG
  • NM_000155.2:c.790_792delinsTAG
  • NM_000155.3:c.790_792delinsTAG
  • NM_000155.3:c.790_792invCTA
  • M60091.1:c.[790delC;792_793insG]
Protein change:
L155*
Molecular consequence:
  • NM_000155.4:c.790_792inv - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001258332.2:c.463_465inv - 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
SCV000631391Invitaecriteria provided, single submitter
Pathogenic
(Jun 27, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000695704Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Dec 19, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

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

Molecular analysis in newborns from Texas affected with galactosemia.

Yang YP, Corley N, Garcia-Heras J.

Hum Mutat. 2002 Jan;19(1):82-3.

PubMed [citation]
PMID:
11754113
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000631391.1

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

Description

This sequence change deletes 3 nucleotide and inserts 3 nucleotides in exon 8 of the GALT mRNA (c.790_792invCTA), creating a premature translational stop signal (p.Leu264*) and 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 particular variant has been reported in the literature in several individuals affected with galactosemia (PMID: 11754113, 11261429, Invitae). For these reasons, this variant has been classified as Pathogenic.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695704.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: GALT c.790_792delinsTAG (p.Leu264X) 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 was absent in 245500 control chromosomes. c.790_792delinsTAG has been reported in the literature in individuals affected with Galactosemia (example, Elsas_1998, Yang_2002, Demirbas_2019 and an external laboratory database). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 20, 2021

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