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NM_000162.5(GCK):c.757G>T (p.Val253Phe) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 22, 2017
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:
RCV000519193.1

Allele description

NM_000162.5(GCK):c.757G>T (p.Val253Phe)

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.757G>T (p.Val253Phe)
HGVS:
  • NC_000007.14:g.44147756C>A
  • NG_008847.2:g.55415G>T
  • NM_000162.5:c.757G>TMANE SELECT
  • NM_001354800.1:c.757G>T
  • NM_033507.3:c.760G>T
  • NM_033508.3:c.754G>T
  • NP_000153.1:p.Val253Phe
  • NP_001341729.1:p.Val253Phe
  • NP_277042.1:p.Val254Phe
  • NP_277043.1:p.Val252Phe
  • LRG_1074t1:c.757G>T
  • LRG_1074t2:c.760G>T
  • LRG_1074:g.55415G>T
  • LRG_1074p1:p.Val253Phe
  • LRG_1074p2:p.Val254Phe
  • NC_000007.13:g.44187355C>A
  • NM_000162.3:c.757G>T
Protein change:
V252F
Links:
dbSNP: rs748964205
NCBI 1000 Genomes Browser:
rs748964205
Molecular consequence:
  • NM_000162.5:c.757G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354800.1:c.757G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033507.3:c.760G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033508.3:c.754G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: CN517202

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000618045GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely pathogenic
(Mar 22, 2017) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From GeneDx, SCV000618045.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The V253F variant in the GCK gene has been reported previously in patients with GCK-related MODY (Constantini et al., 2015; Rajab et al., 2015). The V253F variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). It is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants at the same codon (V253L/A) and in nearby residues (E248K, G249S/A, R250C/P, M251V/K/T/I, C252G/R/Y/S, N254H, T255A/I/S, E256K/D, W257R, G258S/R/C/D) have been reported in the Human Gene Mutation Database in association with MODY (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

Last Updated: Apr 23, 2022