U.S. flag

An official website of the United States government

NM_000162.5(GCK):c.483G>A (p.Lys161=) AND Monogenic diabetes

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 26, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV003234538.1

Allele description [Variation Report for NM_000162.5(GCK):c.483G>A (p.Lys161=)]

NM_000162.5(GCK):c.483G>A (p.Lys161=)

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.483G>A (p.Lys161=)
Other names:
NM_000162.5(GCK):c.483G>A; p.Lys161=
HGVS:
  • NC_000007.14:g.44150956C>T
  • NG_008847.2:g.52215G>A
  • NM_000162.5:c.483G>AMANE SELECT
  • NM_001354800.1:c.483G>A
  • NM_033507.3:c.486G>A
  • NM_033508.3:c.480G>A
  • NP_000153.1:p.Lys161=
  • NP_001341729.1:p.Lys161=
  • NP_277042.1:p.Lys162=
  • NP_277043.1:p.Lys160=
  • LRG_1074t1:c.483G>A
  • LRG_1074t2:c.486G>A
  • LRG_1074:g.52215G>A
  • LRG_1074p1:p.Lys161=
  • LRG_1074p2:p.Lys162=
  • NC_000007.13:g.44190555C>T
  • NM_000162.3:c.483G>A
Links:
dbSNP: rs193922302
NCBI 1000 Genomes Browser:
rs193922302
Molecular consequence:
  • NM_000162.5:c.483G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001354800.1:c.483G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_033507.3:c.486G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_033508.3:c.480G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV003932645ClinGen Monogenic Diabetes Variant Curation Expert Panel
reviewed by expert panel

(ClinGen Diabetes ACMG Specifications GCK V1.1.0)		Pathogenic
(May 26, 2023) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Monogenic Diabetes Variant Curation Expert Panel, SCV003932645.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.483G>A variant in the glucokinase gene, GCK, is a synonymous (silent) variant at codon 161 (p.(Lys161=)) of NM_000162.5. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). It is predicted by SpliceAI to impact splicing (SpliceAI score of 0.85 for donor gain and 0.52 for donor loss, which are greater than the MDEP cutoff of 0.2) (PP3), and there is evidence from RNA studies that this variant results in aberrant splicing, indicating that this variant impacts protein function (PS3; Internal lab contributor). This variant was identified in five unrelated individuals with mildly elevated HbA1c that did not require treatment, and segregated with the phenotype, with four informative meioses in three families (PS4_Moderate, PP1_Strong; PMID: 1956454, Internal lab contributors). In summary, c.483G>A meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.1, approved 3/23/23): PM2_Supporting, PP3, PS4_Moderate, PP1_Strong, PS3.

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

Last Updated: May 7, 2024