NM_000162.5(GCK):c.1113C>A (p.Cys371Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 24, 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:: RCV001662802.6

Allele description [Variation Report for NM_000162.5(GCK):c.1113C>A (p.Cys371Ter)]

NM_000162.5(GCK):c.1113C>A (p.Cys371Ter)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1113C>A (p.Cys371Ter)

Other names:

NM_000162.5(GCK):c.1113C>A; p.Cys371Ter

HGVS:

NC_000007.14:g.44145637G>T
NG_008847.2:g.57534C>A
NM_000162.5:c.1113C>AMANE SELECT
NM_001354800.1:c.1113C>A
NM_001354801.1:c.102C>A
NM_001354802.1:c.-28C>A
NM_001354803.2:c.147C>A
NM_033507.3:c.1116C>A
NM_033508.3:c.1110C>A
NP_000153.1:p.Cys371Ter
NP_001341729.1:p.Cys371Ter
NP_001341730.1:p.Cys34Ter
NP_001341732.1:p.Cys49Ter
NP_277042.1:p.Cys372Ter
NP_277043.1:p.Cys370Ter
LRG_1074t1:c.1113C>A
LRG_1074t2:c.1116C>A
LRG_1074:g.57534C>A
LRG_1074p1:p.Cys371Ter
LRG_1074p2:p.Cys372Ter
NC_000007.13:g.44185236G>T
NM_000162.3:c.1113C>A

Protein change:

C34*

Links:

dbSNP: rs556581174

NCBI 1000 Genomes Browser:

rs556581174

Molecular consequence:

NM_001354802.1:c.-28C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000162.5:c.1113C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354800.1:c.1113C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354801.1:c.102C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001354803.2:c.147C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_033507.3:c.1116C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_033508.3:c.1110C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001880625	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics criteria)	Pathogenic (Dec 11, 2020)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31063852, 26467025
SCV002240116	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 24, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 7553875, 9867845, 14578306, 24323243, 25015100, 25555642, 31063852, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001880625

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics criteria)

Pathogenic
(Dec 11, 2020)

unknown

clinical testing

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

SCV002240116

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 24, 2023)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis.

Grupe A, Hultgren B, Ryan A, Ma YH, Bauer M, Stewart TA.

Cell. 1995 Oct 6;83(1):69-78.

PubMed [citation]

PMID:: 7553875

See all PubMed Citations (9)

Details of each submission

From Athena Diagnostics, SCV001880625.1

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

Description

This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene.

#	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 Invitae, SCV002240116.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Cys371*) in the GCK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GCK are known to be pathogenic (PMID: 7553875, 9867845, 14578306, 24323243, 25015100). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with maturity onset diabetes of the young (PMID: 25555642, 31063852). ClinVar contains an entry for this variant (Variation ID: 617645). For these reasons, this variant has been classified as 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: May 7, 2024

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