GeneBe

7-44189469-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000476008.1(GCK):​n.480+8222G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GCK
ENST00000476008.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.555

Publications

0 publications found
Variant links:
Genes affected
GCK (HGNC:4195): (glucokinase) This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. The use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia. [provided by RefSeq, Aug 2017]
GCK Gene-Disease associations (from GenCC):
  • hyperinsulinism due to glucokinase deficiency
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
  • maturity-onset diabetes of the young type 2
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
  • monogenic diabetes
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • diabetes mellitus, noninsulin-dependent
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • permanent neonatal diabetes mellitus 1
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • transient neonatal diabetes mellitus
    Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
  • maturity-onset diabetes of the young
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • permanent neonatal diabetes mellitus
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GCKNM_000162.5 linkc.-516G>T upstream_gene_variant ENST00000403799.8 NP_000153.1
GCKNM_001354800.1 linkc.-516G>T upstream_gene_variant NP_001341729.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GCKENST00000403799.8 linkc.-516G>T upstream_gene_variant 1 NM_000162.5 ENSP00000384247.3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
47858
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
24760
African (AFR)
AF:
0.00
AC:
0
AN:
1794
American (AMR)
AF:
0.00
AC:
0
AN:
3712
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
948
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3162
South Asian (SAS)
AF:
0.00
AC:
0
AN:
5878
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
1636
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
154
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
28200
Other (OTH)
AF:
0.00
AC:
0
AN:
2374
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.24
CADD
Benign
15
DANN
Benign
0.76
PhyloP100
0.56
PromoterAI
0.0053
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1799884; hg19: chr7-44229068; API