ClinVar Genomic variation as it relates to human health
NM_001008216.2(GALE):c.905G>A (p.Gly302Asp)
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
-
NM_001008216.2(GALE):c.905G>A (p.Gly302Asp)
Variation ID: 21173 Accession: VCV000021173.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 1p36.11 1: 23796234 (GRCh38) [ NCBI UCSC ] 1: 24122724 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Sep 16, 2024 Jun 18, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001008216.2:c.905G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001008217.1:p.Gly302Asp missense NM_000403.4:c.905G>A NP_000394.2:p.Gly302Asp missense NM_001127621.2:c.905G>A NP_001121093.1:p.Gly302Asp missense NC_000001.11:g.23796234C>T NC_000001.10:g.24122724C>T NG_007068.1:g.9571G>A Q14376:p.Gly302Asp - Protein change
- G302D
- Other names
- -
- Canonical SPDI
- NC_000001.11:23796233:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
GALE | - | - |
GRCh38 GRCh37 |
361 | 382 |
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. |
---|---|---|---|---|
Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jun 18, 2024 | RCV000020295.7 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Oct 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
UDPglucose-4-epimerase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004276153.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 302 of the GALE protein … (more)
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 302 of the GALE protein (p.Gly302Asp). This variant is present in population databases (rs137853861, gnomAD 0.02%). This missense change has been observed in individual(s) with galactose epimerase deficiency (PMID: 16301867). ClinVar contains an entry for this variant (Variation ID: 21173). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALE protein function. Experimental studies have shown that this missense change affects GALE function (PMID: 19250319). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
|
|
Likely pathogenic
(Jun 18, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
UDPglucose-4-epimerase deficiency
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005204677.1
First in ClinVar: Sep 16, 2024 Last updated: Sep 16, 2024 |
Comment:
Variant summary: GALE c.905G>A (p.Gly302Asp) 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.905G>A (p.Gly302Asp) 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. The variant allele was found at a frequency of 2e-05 in 251262 control chromosomes. c.905G>A has been reported in the literature in the heterozygous state or presumed compound heterozygous state in at least 2 individuals affected with UDPglucose-4-Epimerase Deficiency or testing positive on a newborn screen (example, Park_2016, Park_2005). These data indicate that the variant may be associated with disease. Enzyme activity was undetectable in vitro (example, Bang_2009). The following publications have been ascertained in the context of this evaluation (PMID: 19250319, 27578510, 16301867). ClinVar contains an entry for this variant (Variation ID: 21173). Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
UDPglucose-4-epimerase deficiency
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV000040660.3
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
|
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 |
---|---|---|---|---|
Epimerase Deficiency Galactosemia. | Adam MP | - | 2021 | PMID: 21290786 |
A Population-Based Genomic Study of Inherited Metabolic Diseases Detected Through Newborn Screening. | Park KJ | Annals of laboratory medicine | 2016 | PMID: 27578510 |
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 rs137853861 ...
HelpRecord last updated Sep 29, 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.