PP4, PM2, PM3, PVS1
ClinVar Genomic variation as it relates to human health
NM_000155.4(GALT):c.634C>T (p.Gln212Ter)
Germline
Classification
Help
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.
(6)
Help
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.
Pathogenic/Likely pathogenic
6
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000155.4(GALT):c.634C>T (p.Gln212Ter)
Variation ID: 25234 Accession: VCV000025234.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9p13.3 9: 34648403 (GRCh38) [ NCBI UCSC ] 9: 34648400 (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 17, 2024 Mar 20, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000155.4:c.634C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000146.2:p.Gln212Ter nonsense NM_001258332.2:c.307C>T NP_001245261.1:p.Gln103Ter nonsense NC_000009.12:g.34648403C>T NC_000009.11:g.34648400C>T NG_009029.2:g.6815C>T NG_028966.1:g.1219C>T - Protein change
- Q212*, Q103*
- Other names
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- Canonical SPDI
- NC_000009.12:34648402: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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.00000
- Links
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. |
|||
| GALT | - | - |
GRCh38 GRCh37 |
718 | 882 | |
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 20, 2024 | RCV000022170.18 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 14, 2023 | RCV000723558.5 |
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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|---|---|---|---|---|---|
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Likely pathogenic
(Dec 18, 2014)
|
criteria provided, single submitter
Method: literature only
|
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220970.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Mar 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226594.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP4, PM2, PM3, PVS1
Number of individuals with the variant: 2
|
|
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Pathogenic
(Dec 22, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002214759.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with galactosemia (PMID: 8522334). ClinVar contains an entry … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with galactosemia (PMID: 8522334). ClinVar contains an entry for this variant (Variation ID: 25234). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln212*) in the GALT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367). (less)
|
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Pathogenic
(Mar 20, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004198524.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Nov 19, 2012)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000110070.8
First in ClinVar: Jan 17, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Dec 23, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002819759.1
First in ClinVar: Jan 15, 2023 Last updated: Jan 15, 2023 |
Comment:
Variant summary: GALT c.634C>T (p.Gln212X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: GALT c.634C>T (p.Gln212X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251472 control chromosomes (gnomAD). c.634C>T has been reported in the literature in compound heterozygous state in multiple individuals affected with Galactosemia (e.g. Gathof_1995, Yuzyuk_2018), where the complete lack of enzyme activity was noted in patient derived red blood cells. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
Comment:
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with galactosemia (PMID: 8522334). ClinVar contains an entry for this variant (Variation ID: 25234). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln212*) in the GALT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367).
Comment:
Variant summary: GALT c.634C>T (p.Gln212X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251472 control chromosomes (gnomAD). c.634C>T has been reported in the literature in compound heterozygous state in multiple individuals affected with Galactosemia (e.g. Gathof_1995, Yuzyuk_2018), where the complete lack of enzyme activity was noted in patient derived red blood cells. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
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. |
Comment:
PP4, PM2, PM3, PVS1
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with galactosemia (PMID: 8522334). ClinVar contains an entry for this variant (Variation ID: 25234). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln212*) in the GALT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367).
Comment:
Variant summary: GALT c.634C>T (p.Gln212X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251472 control chromosomes (gnomAD). c.634C>T has been reported in the literature in compound heterozygous state in multiple individuals affected with Galactosemia (e.g. Gathof_1995, Yuzyuk_2018), where the complete lack of enzyme activity was noted in patient derived red blood cells. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Effect of genotype on galactose-1-phosphate in classic galactosemia patients. | Yuzyuk T | Molecular genetics and metabolism | 2018 | PMID: 30172461 |
| Mutation spectrum in the French cohort of galactosemic patients and structural simulation of 27 novel missense variations. | Boutron A | Molecular genetics and metabolism | 2012 | PMID: 22944367 |
| Combination of enzyme analysis, allele-specific PCR and sequencing to detect mutations in the GALT gene. | Calderon FR | Journal of inherited metabolic disease | 2007 | PMID: 17876724 |
| Molecular and biochemical basis for variants and deficiency of GALT: report of 4 novel mutations. | Shin YS | Bratislavske lekarske listy | 2004 | PMID: 15633893 |
| Molecular heterogeneity of classical and Duarte galactosemia: mutation analysis by denaturing gradient gel electrophoresis. | Greber-Platzer S | Human mutation | 1997 | PMID: 9222760 |
| Characterization of two stop codon mutations in the galactose-1-phosphate uridyltransferase gene of three male galactosemic patients with severe clinical manifestation. | Gathof BS | Human genetics | 1995 | PMID: 8522334 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GALT | - | - | - | - |
Text-mined citations for rs111033746 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record 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.