NM_000162.5(GCK):c.394G>A (p.Asp132Asn) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 15, 2023
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:: RCV003230652.3

Allele description [Variation Report for NM_000162.5(GCK):c.394G>A (p.Asp132Asn)]

NM_000162.5(GCK):c.394G>A (p.Asp132Asn)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.394G>A (p.Asp132Asn)

HGVS:

NC_000007.14:g.44151045C>T
NG_008847.2:g.52126G>A
NM_000162.5:c.394G>AMANE SELECT
NM_001354800.1:c.394G>A
NM_033507.3:c.397G>A
NM_033508.3:c.391G>A
NP_000153.1:p.Asp132Asn
NP_001341729.1:p.Asp132Asn
NP_277042.1:p.Asp133Asn
NP_277043.1:p.Asp131Asn
LRG_1074t1:c.394G>A
LRG_1074t2:c.397G>A
LRG_1074:g.52126G>A
LRG_1074p1:p.Asp132Asn
LRG_1074p2:p.Asp133Asn
NC_000007.13:g.44190644C>T
NM_000162.3:c.394G>A

Protein change:

D131N

Links:

dbSNP: rs762419802

NCBI 1000 Genomes Browser:

rs762419802

Molecular consequence:

NM_000162.5:c.394G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.394G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.397G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.391G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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LOC112757768 [Arachis hypogaea]
LOC112757768 [Arachis hypogaea]
Gene ID:112757768

Gene
LOC116113190 [Pistacia vera]
LOC116113190 [Pistacia vera]
Gene ID:116113190

Gene
LOC116117257 [Pistacia vera]
LOC116117257 [Pistacia vera]
Gene ID:116117257

Gene
RE64336p [Drosophila melanogaster]
RE64336p [Drosophila melanogaster]
gi|145587068|gb|ABP87897.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003928821	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Apr 15, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18382660, 24097065, 29207974 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003928821

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Apr 15, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Glucokinase gene mutations: structural and genotype-phenotype analyses in MODY children from South Italy.

Tinto N, Zagari A, Capuano M, De Simone A, Capobianco V, Daniele G, Giugliano M, Spadaro R, Franzese A, Sacchetti L.

PLoS One. 2008 Apr 2;3(4):e1870. doi: 10.1371/journal.pone.0001870.

PubMed [citation]

PMID:: 18382660
PMCID:: PMC2270336

Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes.

Flannick J, Beer NL, Bick AG, Agarwala V, Molnes J, Gupta N, Burtt NP, Florez JC, Meigs JB, Taylor H, Lyssenko V, Irgens H, Fox E, Burslem F, Johansson S, Brosnan MJ, Trimmer JK, Newton-Cheh C, Tuomi T, Molven A, Wilson JG, O'Donnell CJ, et al.

Nat Genet. 2013 Nov;45(11):1380-5. doi: 10.1038/ng.2794. Epub 2013 Oct 6.

PubMed [citation]

PMID:: 24097065
PMCID:: PMC4051627

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003928821.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: GCK c.394G>A (p.Asp132Asn) results in a conservative amino acid change located in the Hexokinase, N-terminal domain (IPR022672) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251338 control chromosomes (gnomAD). c.394G>A has been reported in the literature in individuals affected with Diabetes (Tinto_2008, Bansal_2017), and has been found segregating with disease in one family (Tinto_2008). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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