NM_000155.4(GALT):c.626A>G (p.Tyr209Cys) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 29, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
5 submissions [Details]
Record status:
current
Accession:
RCV000022167.16

Allele description [Variation Report for NM_000155.4(GALT):c.626A>G (p.Tyr209Cys)]

NM_000155.4(GALT):c.626A>G (p.Tyr209Cys)

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.626A>G (p.Tyr209Cys)
Other names:
p.Y209C:TAT>TGT
HGVS:
  • NC_000009.12:g.34648395A>G
  • NG_009029.2:g.6807A>G
  • NG_028966.1:g.1211A>G
  • NM_000155.4:c.626A>GMANE SELECT
  • NM_001258332.2:c.299A>G
  • NP_000146.2:p.Tyr209Cys
  • NP_000146.2:p.Tyr209Cys
  • NP_001245261.1:p.Tyr100Cys
  • NC_000009.11:g.34648392A>G
  • NM_000155.1:c.626A>G
  • NM_000155.2:c.626A>G
  • NM_000155.3:c.626A>G
  • P07902:p.Tyr209Cys
Protein change:
Y100C
Links:
Genetic Testing Registry (GTR): GTR000500501; UniProtKB: P07902#VAR_002596; dbSNP: rs111033744
NCBI 1000 Genomes Browser:
rs111033744
Molecular consequence:
  • NM_000155.4:c.626A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258332.2:c.299A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000052471Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
pathogenic
(Aug 18, 2011)
germlinecuration, clinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link,

SCV000147998GeneReviewsno assertion criteria providedPathogenic
(Mar 9, 2021)
germlineliterature only

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

SCV000952487Invitaecriteria provided, single submitter
Pathogenic
(Aug 29, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001163243Baylor Geneticscriteria provided, single submitter
Pathogenicgermlineclinical testing

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

SCV001193851Myriad Women's Health, Inc.criteria provided, single submitter
Likely pathogenic
(Dec 13, 2019)
unknownclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes10not providednot provided10not providedcuration
not providedgermlineunknown1not providednot providednot providednot providedclinical testing, literature only
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Combination of enzyme analysis, allele-specific PCR and sequencing to detect mutations in the GALT gene.

Calderon FR, Nelson L, Dobrowolski P, Sinitsyna I, Phansalkar A, Longo N, Pasquali M, Mao R.

J Inherit Metab Dis. 2007 Oct;30(5):818. Epub 2007 Sep 17.

PubMed [citation]
PMID:
17876724

Characterization of an unusual deletion of the galactose-1-phosphate uridyl transferase (GALT) gene.

Coffee B, Hjelm LN, DeLorenzo A, Courtney EM, Yu C, Muralidharan K.

Genet Med. 2006 Oct;8(10):635-40.

PubMed [citation]
PMID:
17079880
See all PubMed Citations (17)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000052471.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providednot providedcuration PubMed (11)
2not provided1not providednot providedcuration PubMed (11)
3not provided1not providednot providedcuration PubMed (11)
4not provided2not providednot providedcuration PubMed (11)
5not provided1not providednot providedcuration PubMed (11)
6not providednot providednot providednot providedclinical testing PubMed (11)

Description

"The variant was detected in 5 alleles in a GALT pt cohort; the authors report the variant is a common mutation found in Caucasians; controls not tested."
"A pt clinically diagnosed with GALT is compound heterozygous for the variant and Q118R(DV); the authors list the phenotype of the pt as severe; controls not tested."
"A patient, age 3, diagnosed with GALT is compound heterozygous for the variant and R258C; authorship overlap with Elsas_GALT_Genet Med_1998 and Palmieri_GALT_Metabolism_1999, but this genotype was not previously reported; the authors report that the pt, “had greater than 5% residual activity and a Duarte-like isoelectric focusing banding pattern”; authors did not determine if the variant occurred in controls."

Two siblings diagnosed with GALT are compound heterozygous for the variant and Q188R(DV); controls not tested.

A GALT clinical sample was determined to be compound heterozygous for the variant and Q188R (DV); unknown if detected in controls.

Description

Converted during submission to Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes5not providednot provided5not providednot providednot provided
2germlineyes1not providednot provided1not providednot providednot provided
3germlineyes1not providednot provided1not providednot providednot provided
4germlineyes2not providednot provided2not providednot providednot provided
5germlineyes1not providednot provided1not providednot providednot provided
6germlineunknownnot providedBloodassert pathogenicitynot providednot providednot provided See 6

Co-occurrences

#ZygosityAllelesNumber of Observations
6SingleHeterozygoteGALT:c.940A>G, GALT:c.-119_-116delGTCA1

From GeneReviews, SCV000147998.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

Severe classic pathogenic variant

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

From Invitae, SCV000952487.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces tyrosine with cysteine at codon 209 of the GALT protein (p.Tyr209Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs111033744, ExAC 0.006%). This variant has been observed in several individuals affected with galactosemia (PMID: 11397328, 16540753, 10399107). ClinVar contains an entry for this variant (Variation ID: 25231). Experimental studies have shown that this missense change reduces GALT enzymatic activity (PMID: 22743281). This variant disrupts the p.Tyr209 amino acid residue in GALT. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 10399107), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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

From Baylor Genetics, SCV001163243.1

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

From Myriad Women's Health, Inc., SCV001193851.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

NM_000155.3(GALT):c.626A>G(Y209C) is classified as likely pathogenic in the context of galactosemia. Sources cited for classification include the following: PMID 12595586, 10960497, 22693313, 11261429, 10399107 and 22743281. Classification of NM_000155.3(GALT):c.626A>G(Y209C) is based on the following criteria: This variant has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.

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

Last Updated: Nov 20, 2021

Support Center