NM_000162.5(GCK):c.1339del (p.Arg447fs) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 21, 2016
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:: RCV000481054.2

Allele description [Variation Report for NM_000162.5(GCK):c.1339del (p.Arg447fs)]

NM_000162.5(GCK):c.1339del (p.Arg447fs)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1339del (p.Arg447fs)

Other names:

NM_000162.5(GCK):c.1339del; p.Arg447fs

HGVS:

NC_000007.14:g.44145196del
NG_008847.2:g.57976del
NM_000162.5:c.1339delMANE SELECT
NM_001354800.1:c.1339del
NM_001354801.1:c.328del
NM_001354802.1:c.199del
NM_001354803.2:c.373del
NM_033507.3:c.1342del
NM_033508.3:c.1336del
NP_000153.1:p.Arg447fs
NP_001341729.1:p.Arg447fs
NP_001341730.1:p.Arg110fs
NP_001341731.1:p.Arg67fs
NP_001341732.1:p.Arg125fs
NP_277042.1:p.Arg448fs
NP_277043.1:p.Arg446fs
LRG_1074t1:c.1339del
LRG_1074t2:c.1342del
LRG_1074:g.57976del
LRG_1074p1:p.Arg447fs
LRG_1074p2:p.Arg448fs
NC_000007.13:g.44184795del
NM_000162.3:c.1339delC

Protein change:

R110fs

Links:

dbSNP: rs1064795242

NCBI 1000 Genomes Browser:

rs1064795242

Molecular consequence:

NM_000162.5:c.1339del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354800.1:c.1339del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354801.1:c.328del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354802.1:c.199del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354803.2:c.373del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033507.3:c.1342del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033508.3:c.1336del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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DNAJC1 DnaJ heat shock protein family (Hsp40) member C1 [Homo sapiens]
DNAJC1 DnaJ heat shock protein family (Hsp40) member C1 [Homo sapiens]
Gene ID:64215

Gene
64215[uid] AND (alive[prop]) (1)
Gene
Or4d5 olfactory receptor family 4 subfamily D member 5 [Mus musculus]
Or4d5 olfactory receptor family 4 subfamily D member 5 [Mus musculus]
Gene ID:258601

Gene
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Accession: GDS5826

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000570866	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Jul 21, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000570866

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Jul 21, 2016)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000570866.4

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

Description

The c.1339delC variant in the GCK gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It causes a frameshift starting with codon Arginine 447, changes this amino acid to a Glycine residue and creates a Stop codon at position 167 of the new reading frame, denoted p.Arg447GlyfsX167. c.1339delC was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, this variant is not predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay, as it results in protein extension. The variant leads to the final 19 amino acids being replaced by 166 incorrect amino acids. The final 19 amino acids replaced by this variant are important in stabilizing the active and inactive forms of the protein (Molnes et al., 2008). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

Last Updated: Sep 16, 2023

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