ClinVar Genomic variation as it relates to human health
NM_001008216.2(GALE):c.715C>T (p.Arg239Trp)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001008216.2(GALE):c.715C>T (p.Arg239Trp)
Variation ID: 21172 Accession: VCV000021172.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.11 1: 23796777 (GRCh38) [ NCBI UCSC ] 1: 24123267 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Jun 24, 2023 May 5, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001008216.2:c.715C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001008217.1:p.Arg239Trp missense NM_000403.4:c.715C>T NP_000394.2:p.Arg239Trp missense NM_001127621.2:c.715C>T NP_001121093.1:p.Arg239Trp missense NC_000001.11:g.23796777G>A NC_000001.10:g.24123267G>A NG_007068.1:g.9028C>T Q14376:p.Arg239Trp - Protein change
- R239W
- Other names
- -
- Canonical SPDI
- NC_000001.11:23796776:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
1000 Genomes Project 0.00020
1000 Genomes Project 30x 0.00031
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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GALE | - | - |
GRCh38 GRCh37 |
357 | 374 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 5, 2023 | RCV000020294.6 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Mar 18, 2016)
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criteria provided, single submitter
Method: reference population
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UDPglucose-4-epimerase deficiency
Affected status: unknown
Allele origin:
germline
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Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center
Accession: SCV000267331.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Number of individuals with the variant: 1
Age: 40-69 years
Ethnicity/Population group: East Asian
Geographic origin: South Korean
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Pathogenic
(May 05, 2023)
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criteria provided, single submitter
Method: clinical testing
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UDPglucose-4-epimerase deficiency
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003934495.1
First in ClinVar: Jun 24, 2023 Last updated: Jun 24, 2023 |
Comment:
Variant summary: GALE c.715C>T (p.Arg239Trp) results in a non-conservative amino acid change located in the NAD(P)-binding domain (IPR016040) of the encoded protein sequence. Five of … (more)
Variant summary: GALE c.715C>T (p.Arg239Trp) results in a non-conservative amino acid change located in the NAD(P)-binding domain (IPR016040) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. This is supported by molecular dynamics, residue network analysis, and cross-correlation matrix based computational strategies (Kumar_2019) supporting a critical amino acid residue essential for UDP-galactose 4-epimerase enzyme function. The variant allele was found at a frequency of 1.6e-05 in 243976 control chromosomes. c.715C>T has been reported in the literature as a biallelic genotype in individuals affected with UDPglucose-4-Epimerase Deficiency (example Park_2005). At least one publication reports experimental evidence evaluating an impact on protein function (Bang_2009). The most pronounced variant effect results in no detectable enzyme activity when expressed in GALE-null ldlD cells. Also unlike wild-type, this variant was not able to rescue galactose-sensitive cell proliferation when stably expressed in ldlD cells. The following publications have been ascertained in the context of this evaluation (PMID: 19250319, 33555556, 16301867, 30247636). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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not provided
(-)
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no classification provided
Method: literature only
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UDPglucose-4-epimerase deficiency
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000040658.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
Comment:
Account for 67% of alleles reported in a cohort of asymptomatic Koreans with peripheral epimerase deficiency galactosemia
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Molecular dynamics, residue network analysis, and cross-correlation matrix to characterize the deleterious missense mutations in GALE causing galactosemia III. | Kumar SU | Cell biochemistry and biophysics | 2021 | PMID: 33555556 |
Epimerase Deficiency Galactosemia. | Adam MP | - | 2021 | PMID: 21290786 |
Inherited thrombocytopenia associated with mutation of UDP-galactose-4-epimerase (GALE). | Seo A | Human molecular genetics | 2019 | PMID: 30247636 |
In silico prediction of the effects of mutations in the human UDP-galactose 4'-epimerase gene: towards a predictive framework for type III galactosemia. | McCorvie TJ | Gene | 2013 | PMID: 23644136 |
Functional analysis of mutations in UDP-galactose-4-epimerase (GALE) associated with galactosemia in Korean patients using mammalian GALE-null cells. | Bang YL | The FEBS journal | 2009 | PMID: 19250319 |
The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency galactosemia in Korean patients. | Park HD | Genetics in medicine : official journal of the American College of Medical Genetics | 2005 | PMID: 16301867 |
Text-mined citations for rs137853860 ...
HelpRecord last updated Dec 25, 2023
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.