NM_000154.2(GALK1):c.94G>A (p.Val32Met) AND Deficiency of galactokinase

Clinical significance:Uncertain significance (Last evaluated: May 18, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000005982.5

Allele description [Variation Report for NM_000154.2(GALK1):c.94G>A (p.Val32Met)]

NM_000154.2(GALK1):c.94G>A (p.Val32Met)

Gene:
GALK1:galactokinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q25.1
Genomic location:
Preferred name:
NM_000154.2(GALK1):c.94G>A (p.Val32Met)
HGVS:
  • NC_000017.11:g.75765043C>T
  • NG_008079.1:g.5157G>A
  • NM_000154.2:c.94G>AMANE SELECT
  • NP_000145.1:p.Val32Met
  • LRG_1430t1:c.94G>A
  • LRG_1430p1:p.Val32Met
  • NC_000017.10:g.73761124C>T
  • NM_000154.1:c.94G>A
  • P51570:p.Val32Met
Protein change:
V32M; VAL32MET
Links:
UniProtKB: P51570#VAR_002547; OMIM: 604313.0001; dbSNP: rs104894576
NCBI 1000 Genomes Browser:
rs104894576
Molecular consequence:
  • NM_000154.2:c.94G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Deficiency of galactokinase (GALAC2)
Synonyms:
GALACTOSEMIA II; Galactosemia 2; Hereditary galactokinase deficiency
Identifiers:
MONDO: MONDO:0009255; MedGen: C0268155; Orphanet: 352; OMIM: 230200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000026164OMIMno assertion criteria providedPathogenic
(Jul 1, 1995)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000800515Counsylcriteria provided, single submitter
Uncertain significance
(Apr 6, 2017)
unknownclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV001379141Invitaecriteria provided, single submitter
Uncertain significance
(Sep 24, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001653398Nilou-Genome Labcriteria provided, single submitter
Uncertain significance
(May 18, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Biochemical characterization of two GALK1 mutations in patients with galactokinase deficiency.

Sangiuolo F, Magnani M, Stambolian D, Novelli G.

Hum Mutat. 2004 Apr;23(4):396.

PubMed [citation]
PMID:
15024738

A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies).

Kalaydjieva L, Perez-Lezaun A, Angelicheva D, Onengut S, Dye D, Bosshard NU, Jordanova A, Savov A, Yanakiev P, Kremensky I, Radeva B, Hallmayer J, Markov A, Nedkova V, Tournev I, Aneva L, Gitzelmann R.

Am J Hum Genet. 1999 Nov;65(5):1299-307.

PubMed [citation]
PMID:
10521295
PMCID:
PMC1288282
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000026164.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a child with galactokinase deficiency and congenital cataracts (GALAC2; 230200), Stambolian et al. (1995) identified a homozygous 94G-A transition in the GALK1 gene, resulting in a val32-to-met (V32M) substitution. In vitro functional expression studies showed that the V32M mutation resulted in significantly decreased enzyme activity.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV000800515.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001379141.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces valine with methionine at codon 32 of the GALK1 protein (p.Val32Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual affected with galactokinase deficiency (PMID: 7670469). ClinVar contains an entry for this variant (Variation ID: 5628). This variant has been reported to affect GALK1 protein function (PMID: 7670469, 12694189). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Nilou-Genome Lab, SCV001653398.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 3, 2021

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