ClinVar Genomic variation as it relates to human health
NM_000154.2(GALK1):c.82C>A (p.Pro28Thr)
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_000154.2(GALK1):c.82C>A (p.Pro28Thr)
Variation ID: 5630 Accession: VCV000005630.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q25.1 17: 75765055 (GRCh38) [ NCBI UCSC ] 17: 73761136 (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 Nov 17, 2024 Nov 15, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000154.2:c.82C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000145.1:p.Pro28Thr missense NC_000017.11:g.75765055G>T NC_000017.10:g.73761136G>T NG_008079.1:g.5145C>A LRG_1430t1:c.82C>A LRG_1430p1:p.Pro28Thr P51570:p.Pro28Thr - Protein change
- P28T
- Other names
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- Canonical SPDI
- NC_000017.11:75765054:G: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
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The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00003
- 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 | ||
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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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| GALK1 | - | - |
GRCh38 GRCh37 |
489 | 985 | |
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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| Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Nov 15, 2024 | RCV000005984.19 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 13, 2022 | RCV002262559.16 |
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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Pathogenic
(Dec 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of galactokinase
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002789660.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Aug 22, 2019)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of galactokinase
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002024146.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jul 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of galactokinase
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000792779.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
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Pathogenic
(Oct 13, 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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GeneDx
Accession: SCV003918246.1
First in ClinVar: Apr 23, 2023 Last updated: Apr 23, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21264483, 29893426, 31589614, 7670469, 12694189, 10521295, 32807972) (less)
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Pathogenic
(Apr 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of galactokinase
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000822531.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 20, 2024 |
Comment:
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD … (more)
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 28 of the GALK1 protein (p.Pro28Thr). This missense change has been observed in individuals with galactokinase deficiency (PMID: 10521295, 10790206, 11978883, 11978884, 12647253, 21290184). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GALK1 function (PMID: 10790206). 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 not expected to disrupt GALK1 protein function. ClinVar contains an entry for this variant (Variation ID: 5630). (less)
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Pathogenic
(Feb 12, 2024)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of galactokinase
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004197941.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Apr 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002545974.16
First in ClinVar: Jul 09, 2022 Last updated: Oct 20, 2024 |
Comment:
GALK1: PP1:Strong, PP4:Strong, PM2, PS3:Supporting
Number of individuals with the variant: 1
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Pathogenic
(Nov 15, 2024)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of galactokinase
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Department of Human Genetics, Hannover Medical School
Accession: SCV005397905.1
First in ClinVar: Nov 17, 2024 Last updated: Nov 17, 2024 |
Comment:
ACMG: PS3_Supporting, PM2_Supporting, PM3, PP1_Supporting, PP3, PP4_Strong
Clinical Features:
Reduced erythrocyte galactokinase activity (present)
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Pathogenic
(Oct 01, 2004)
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no assertion criteria provided
Method: literature only
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GALACTOSEMIA II
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026166.2
First in ClinVar: Apr 04, 2013 Last updated: May 04, 2020 |
Comment on evidence:
In affected members from 6 Romani (Gypsy) families from Bulgaria with galactokinase deficiency (GALAC2; 230200), Kalaydjieva et al. (1999) identified a homozygous 563C-A transversion in … (more)
In affected members from 6 Romani (Gypsy) families from Bulgaria with galactokinase deficiency (GALAC2; 230200), Kalaydjieva et al. (1999) identified a homozygous 563C-A transversion in the GALK1 gene, resulting in a pro28-to-thr (P28T) mutation. The P28T carrier rate in this endogamous population is approximately 5%. The authors concluded that this mutation was most likely responsible for the galactokinase deficiency in the cases originally described by Gitzelmann (1967). Kolosha et al. (2000) found the P28T mutation in homozygous form in an affected 5-day-old male infant of Turkish extraction. Morar et al. (2004) used the P28T mutation and 4 other private mutations among the Roma (Gypsies) to infer some of the missing parameters relevant to the comprehensive characterization of the population history of the Gypsies. Sharing of mutations and high carrier rates supported a strong founder effect. (less)
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Pathogenic
(Sep 28, 2021)
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no assertion criteria provided
Method: clinical testing
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Deficiency of galactokinase
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002089506.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Features and outcome of galactokinase deficiency in children diagnosed by newborn screening. | Hennermann JB | Journal of inherited metabolic disease | 2011 | PMID: 21290184 |
| Mutation history of the roma/gypsies. | Morar B | American journal of human genetics | 2004 | PMID: 15322984 |
| Functional analysis of disease-causing mutations in human galactokinase. | Timson DJ | European journal of biochemistry | 2003 | PMID: 12694189 |
| [Mutation P28T in gene GK1 as the cause of a familial galactokinase deficiency]. | Girós M | Archivos de la Sociedad Espanola de Oftalmologia | 2003 | PMID: 12647253 |
| The P28T mutation in the GALK1 gene accounts for galactokinase deficiency in Roma (Gypsy) patients across Europe. | Hunter M | Pediatric research | 2002 | PMID: 11978884 |
| An unexpectedly high frequency of hypergalactosemia in an immigrant Bosnian population revealed by newborn screening. | Reich S | Pediatric research | 2002 | PMID: 11978883 |
| Novel mutations in 13 probands with galactokinase deficiency. | Kolosha V | Human mutation | 2000 | PMID: 10790206 |
| A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). | Kalaydjieva L | American journal of human genetics | 1999 | PMID: 10521295 |
| Gitzelmann, R. Hereditary galactokinase deficiency, a newly recognized cause of juvenile cataracts. Pediat. Res. 1: 14-23, 1967. | - | - | - | - |
Text-mined citations for rs104894572 ...
HelpRecord last updated Nov 25, 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.