ClinVar Genomic variation as it relates to human health
NM_001008216.2(GALE):c.956G>A (p.Gly319Glu)
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.
Uncertain significance(2); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001008216.2(GALE):c.956G>A (p.Gly319Glu)
Variation ID: 3681 Accession: VCV000003681.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p36.11 1: 23796183 (GRCh38) [ NCBI UCSC ] 1: 24122673 (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 Mar 16, 2024 Jan 4, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001008216.2:c.956G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001008217.1:p.Gly319Glu missense NM_000403.4:c.956G>A NP_000394.2:p.Gly319Glu missense NM_001127621.2:c.956G>A NP_001121093.1:p.Gly319Glu missense NC_000001.11:g.23796183C>T NC_000001.10:g.24122673C>T NG_007068.1:g.9622G>A Q14376:p.Gly319Glu - Protein change
- G319E
- Other names
- -
- Canonical SPDI
- NC_000001.11:23796182:C:T
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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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0.00200 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00035
Exome Aggregation Consortium (ExAC) 0.00043
The Genome Aggregation Database (gnomAD) 0.00121
Trans-Omics for Precision Medicine (TOPMed) 0.00127
1000 Genomes Project 0.00200
1000 Genomes Project 30x 0.00219
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
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
Help
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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Likely benign (3) |
criteria provided, single submitter
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Jan 4, 2024 | RCV000003866.18 | |
Uncertain significance; other (2) |
criteria provided, multiple submitters, no conflicts
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Oct 19, 2022 | RCV000078697.24 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 4, 2024 | RCV003904802.1 |
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
Help
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 benign
(Jan 04, 2024)
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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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Invitae
Accession: SCV001113707.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Uncertain significance
(Jan 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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GALE-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004720272.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The GALE c.956G>A variant is predicted to result in the amino acid substitution p.Gly319Glu. This variant has been reported in two patients with GALE deficiency … (more)
The GALE c.956G>A variant is predicted to result in the amino acid substitution p.Gly319Glu. This variant has been reported in two patients with GALE deficiency in erythrocytes and lymphoblasts; one of them was heterozygous for a second amino acid substitution (p.Ser81Arg) (Openo et al. 2006. PMID 16385452). The authors in this study reported moderate to severe enzyme deficiencies based on in vitro activity assays. In contrast, others have reported that this amino acid change does not significantly affect the kinetics or activity of the GALE enzyme, and may therefore be a neutral polymorphism (Timson. 2005. PubMed ID: 16302980; Wasilenko et al. 2005. PubMed ID: 15639193). This variant has been reported at an allele frequency of ~0.4% in an African population, which is relatively high for a pathogenic variant. While we suspect that this variant may possibly be benign, its clinical significance is uncertain due to the conflicting published evidence. (less)
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other
(Jun 07, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000110557.8
First in ClinVar: Jan 17, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 15
Sex: mixed
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Uncertain significance
(Oct 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV001468004.2
First in ClinVar: Jan 09, 2021 Last updated: Jan 21, 2023 |
Comment:
PS3_Supporting, BA1, PP3
Comment on evidence:
PS3, BS2
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Pathogenic
(Jan 01, 1998)
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no assertion criteria provided
Method: literature only
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GALACTOSEMIA III
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000024031.2
First in ClinVar: Apr 04, 2013 Last updated: May 04, 2020 |
Comment on evidence:
Maceratesi et al. (1998) found that 1 African American patient with galactose epimerase deficiency (GALAC3; 230350) was heterozygous for a GGG-to-GAG transition in the GALE … (more)
Maceratesi et al. (1998) found that 1 African American patient with galactose epimerase deficiency (GALAC3; 230350) was heterozygous for a GGG-to-GAG transition in the GALE gene that changed codon 319 from glycine to glutamic acid (G319E). The other mutation was not identified. (less)
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Pathogenic
(Feb 24, 2021)
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no assertion criteria provided
Method: literature only
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UDPglucose-4-epimerase deficiency
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000040661.2
First in ClinVar: Apr 04, 2013 Last updated: Nov 13, 2021 |
Comment:
Assoc with asymptomatic peripheral epimerase deficiency galactosemia in African Americans
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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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Epimerase Deficiency Galactosemia. | Adam MP | - | 2021 | PMID: 21290786 |
Epimerase-deficiency galactosemia is not a binary condition. | Openo KK | American journal of human genetics | 2006 | PMID: 16385452 |
Functional analysis of disease-causing mutations in human UDP-galactose 4-epimerase. | Timson DJ | The FEBS journal | 2005 | PMID: 16302980 |
Functional characterization of the K257R and G319E-hGALE alleles found in patients with ostensibly peripheral epimerase deficiency galactosemia. | Wasilenko J | Molecular genetics and metabolism | 2005 | PMID: 15639193 |
Human UDP-galactose 4' epimerase (GALE) gene and identification of five missense mutations in patients with epimerase-deficiency galactosemia. | Maceratesi P | Molecular genetics and metabolism | 1998 | PMID: 9538513 |
45:191A | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GALE | - | - | - | - |
J Invest Med. 1997 | - | - | - | - |
Text-mined citations for rs28940885 ...
HelpRecord last updated Apr 15, 2024
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.