NM_000155.4(GALT):c.394C>T (p.His132Tyr) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Apr 17, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000022102.5

Allele description [Variation Report for NM_000155.4(GALT):c.394C>T (p.His132Tyr)]

NM_000155.4(GALT):c.394C>T (p.His132Tyr)

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.394C>T (p.His132Tyr)
HGVS:
  • NC_000009.12:g.34647848C>T
  • NG_009029.2:g.6260C>T
  • NG_028966.1:g.664C>T
  • NM_000155.4:c.394C>TMANE SELECT
  • NM_001258332.2:c.67C>T
  • NP_000146.2:p.His132Tyr
  • NP_001245261.1:p.His23Tyr
  • NC_000009.11:g.34647845C>T
  • NG_009029.1:g.6211C>T
  • NM_000155.3:c.394C>T
  • P07902:p.His132Tyr
Protein change:
H132Y
Links:
UniProtKB: P07902#VAR_002570; dbSNP: rs111033688
NCBI 1000 Genomes Browser:
rs111033688
Molecular consequence:
  • NM_000155.4:c.394C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258332.2:c.67C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000800661Counsylcriteria provided, single submitter
Uncertain significance
(Feb 22, 2018)
unknownclinical testing

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

Citation Link,

SCV001158685ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Apr 17, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

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

Citations

PubMed

Long-term speech and language developmental issues among children with Duarte galactosemia.

Powell KK, Van Naarden Braun K, Singh RH, Shapira SK, Olney RS, Yeargin-Allsopp M.

Genet Med. 2009 Dec;11(12):874-9. doi: 10.1097/GIM.0b013e3181c0c38d.

PubMed [citation]
PMID:
19904210

Clinical profile and molecular characterization of Galactosemia in Brazil: identification of seven novel mutations.

Garcia DF, Camelo JS Jr, Molfetta GA, Turcato M, Souza CF, Porta G, Steiner CE, Silva WA Jr.

BMC Med Genet. 2016 May 12;17(1):39. doi: 10.1186/s12881-016-0300-8.

PubMed [citation]
PMID:
27176039
PMCID:
PMC4866286

Details of each submission

From Counsyl, SCV000800661.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001158685.1

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

Description

The GALT c.394C>T; p.His132Tyr variant (rs367543256) is reported in the in individuals affected with galactosemia (Elsas 1998, Powell 2009). Functional analyses demonstrate reduced enzyme activity when in the compound heterozygous state with the Duarte allele (Powell 2009). This variant is reported in ClinVar (Variation ID: 37357), and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. Additionally, another variant at this codon (c.396C>A; p.His132Gln) has been reported in individuals with galactosemia and is considered pathogenic (Narravula 2017, Tang 2012). The histidine at codon 132 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on available information, this variant is considered to be likely pathogenic. References: Elsas LJ 2nd and Lai K. The molecular biology of galactosemia. Genet Med. 1998 Nov-Dec;1(1):40-8. Powell KK et al. Long-term speech and language developmental issues among children with Duarte galactosemia. Genet Med. 2009 Dec;11(12):874-9. Narravula A Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing. Genet Med. 2017 Jan;19(1):77-82. Tang M et al. Correlation assessment among clinical phenotypes, expression analysis and molecular modeling of 14 novel variations in the human galactose-1-phosphate uridylyltransferase gene. Hum Mutat. 2012 Jul;33(7):1107-15.

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

Last Updated: Nov 27, 2021

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