U.S. flag

An official website of the United States government

NM_000162.5(GCK):c.475A>G (p.Ile159Val) AND Monogenic diabetes

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 1, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV004526193.3

Allele description [Variation Report for NM_000162.5(GCK):c.475A>G (p.Ile159Val)]

NM_000162.5(GCK):c.475A>G (p.Ile159Val)

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.475A>G (p.Ile159Val)
HGVS:
  • NC_000007.14:g.44150964T>C
  • NG_008847.2:g.52207A>G
  • NM_000162.5:c.475A>GMANE SELECT
  • NM_001354800.1:c.475A>G
  • NM_033507.3:c.478A>G
  • NM_033508.3:c.472A>G
  • NP_000153.1:p.Ile159Val
  • NP_001341729.1:p.Ile159Val
  • NP_277042.1:p.Ile160Val
  • NP_277043.1:p.Ile158Val
  • LRG_1074t1:c.475A>G
  • LRG_1074t2:c.478A>G
  • LRG_1074:g.52207A>G
  • LRG_1074p1:p.Ile159Val
  • LRG_1074p2:p.Ile160Val
  • NC_000007.13:g.44190563T>C
  • NM_000162.3:c.475A>G
Protein change:
I158V
Links:
dbSNP: rs1319364468
NCBI 1000 Genomes Browser:
rs1319364468
Molecular consequence:
  • NM_000162.5:c.475A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354800.1:c.475A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033507.3:c.478A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033508.3:c.472A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Monogenic diabetes
Identifiers:
MONDO: MONDO:0015967; MedGen: C3888631

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005040498Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Mar 1, 2024) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Analysis of the GCK gene in 79 MODY type 2 patients: A multicenter Turkish study, mutation profile and description of twenty novel mutations.

Aykut A, Karaca E, Onay H, Gökşen D, Çetinkalp Ş, Eren E, Ersoy B, Çakır EP, Büyükinan M, Kara C, Anık A, Kırel B, Özen S, Atik T, Darcan Ş, Özkınay F.

Gene. 2018 Jan 30;641:186-189. doi: 10.1016/j.gene.2017.10.057. Epub 2017 Oct 19.

PubMed [citation]
PMID:
29056535

Insights into pathogenesis of five novel GCK mutations identified in Chinese MODY patients.

Liu L, Liu Y, Ge X, Liu X, Chen C, Wang Y, Li M, Yin J, Zhang J, Chen Y, Zhang R, Jiang Y, Zhao W, Yang D, Zheng T, Lu M, Zhuang L, Jiang M.

Metabolism. 2018 Dec;89:8-17. doi: 10.1016/j.metabol.2018.09.004. Epub 2018 Sep 23.

PubMed [citation]
PMID:
30257192

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005040498.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: GCK c.475A>G (p.Ile159Val) results in a conservative amino acid change located in the Hexokinase, N-terminal (IPR022672) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251458 control chromosomes. c.475A>G has been reported in the literature in individuals affected with Monogenic Diabetes (Liu_2018, Aykut_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29056535, 30257192). ClinVar contains an entry for this variant (Variation ID: 1679549). Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Jul 7, 2024