NM_000155.4(GALT):c.626A>G (p.Tyr209Cys) AND not provided

Clinical significance:Pathogenic (Last evaluated: Apr 13, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000185918.4

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:
6

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000110069EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(May 6, 2016)
germlineclinical testing

Citation Link,

SCV000238871GeneDxcriteria provided, single submitter
Pathogenic
(Apr 13, 2018)
germlineclinical testing

Citation Link,

SCV000281374Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinicscriteria provided, single submitter
Pathogenic
(Sep 14, 2015)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown6not providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000110069.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided6not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided6not providednot providednot provided

From GeneDx, SCV000238871.9

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

Description

The Y209C variant is a common pathogenic variant in the Caucasian population and has been reported in several unrelated individuals with galactosemia (Elsas et al., 1998; Zekanowski et al., 1999; Malone et al., 2011; Sartippour et al., 2014). Functional analysis of Y209C found that it is associated with significantly reduced, but not absent GALT activity (Liu et al., 2012). The Y209C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The Y209C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. In summary, we interpret Y209C to be a pathogenic variant.

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

From Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics, SCV000281374.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot provided0.000448not providednot provided

Last Updated: Nov 27, 2021

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