NM_000162.5(GCK):c.167A>C (p.Lys56Thr) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Nov 2, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002475236.6

Allele description [Variation Report for NM_000162.5(GCK):c.167A>C (p.Lys56Thr)]

NM_000162.5(GCK):c.167A>C (p.Lys56Thr)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.167A>C (p.Lys56Thr)

Other names:

NM_000162.5(GCK):c.167A>C; p.Lys56Thr

HGVS:

NC_000007.14:g.44153342T>G
NG_008847.2:g.49829A>C
NM_000162.5:c.167A>CMANE SELECT
NM_001354800.1:c.167A>C
NM_033507.3:c.170A>C
NM_033508.3:c.164A>C
NP_000153.1:p.Lys56Thr
NP_001341729.1:p.Lys56Thr
NP_277042.1:p.Lys57Thr
NP_277043.1:p.Lys55Thr
LRG_1074t1:c.167A>C
LRG_1074t2:c.170A>C
LRG_1074:g.49829A>C
LRG_1074p1:p.Lys56Thr
LRG_1074p2:p.Lys57Thr
NC_000007.13:g.44192941T>G
NM_000162.3:c.167A>C

Protein change:

K55T

Molecular consequence:

NM_000162.5:c.167A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.167A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.170A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.164A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

CTD nuclear envelope phosphatase 1 [Homo sapiens]
CTD nuclear envelope phosphatase 1 [Homo sapiens]
gi|31542547|ref|NP_056158.2|

Protein
Homo sapiens ribosomal protein S20 (RPS20), transcript variant 2, mRNA
Homo sapiens ribosomal protein S20 (RPS20), transcript variant 2, mRNA
gi|1813126992|ref|NM_001023.4|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002771542	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Sep 22, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33852230, 26467025
SCV002976106	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33852230, 28492532
SCV004563553	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Nov 2, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002771542

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Sep 22, 2021)

unknown

clinical testing

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

SCV002976106

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 3, 2023)

germline

clinical testing

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

SCV004563553

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain significance
(Nov 2, 2023)

germline

clinical testing

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Frequency and characterization of mutations in genes in a large cohort of patients referred to MODY registry.

Breidbart E, Deng L, Lanzano P, Fan X, Guo J, Leibel RL, LeDuc CA, Chung WK.

J Pediatr Endocrinol Metab. 2021 Apr 13;34(5):633-638. doi: 10.1515/jpem-2020-0501. Print 2021 May 26.

PubMed [citation]

PMID:: 33852230
PMCID:: PMC8970616

See all PubMed Citations (3)

Details of each submission

From Athena Diagnostics, SCV002771542.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002976106.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 56 of the GCK protein (p.Lys56Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant GCK-related conditions (PMID: 33852230). ClinVar contains an entry for this variant (Variation ID: 1807279). 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 GCK protein function. 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.

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004563553.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The GCK c.167A>C; p.Lys56Thr variant is reported in the literature in one individual with suspected maturity-onset diabetes of the young (MODY; Breidbart 2021). This variant is also reported in ClinVar (Variation ID: 1807279) and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. Additionally, another variant at this codon (c.167A>G, p.Lys56Arg) has been reported in individuals with MODY (Campos Franco 2022, Delvecchio 2017). Computational analyses predict that the p.Lys56Thr variant is deleterious (REVEL: 0.957). However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time. References: Breidbart E et al. Frequency and characterization of mutations in genes in a large cohort of patients referred to MODY registry. J Pediatr Endocrinol Metab. 2021 Apr 13;34(5):633-638. PMID: 33852230. Campos Franco P et al. Clinical and genetic characterization and long-term evaluation of individuals with maturity-onset diabetes of the young (MODY): The journey towards appropriate treatment. Diabetes Res Clin Pract. 2022 May;187:109875. PMID: 35472491. Delvecchio M et al. Monogenic Diabetes Accounts for 6.3% of Cases Referred to 15 Italian Pediatric Diabetes Centers During 2007 to 2012. J Clin Endocrinol Metab. 2017 Jun 1;102(6):1826-1834. PMID: 28323911.

#	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 29, 2024

ClinVar

Relating variation to medicine