rs375836361

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001486.4(GCKR):ā€‹c.151C>Gā€‹(p.Arg51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict 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: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

GCKR
NM_001486.4 missense

Scores

4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.542
Variant links:
Genes affected
GCKR (HGNC:4196): (glucokinase regulator) This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of the young (MODY). [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30486482).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GCKRNM_001486.4 linkc.151C>G p.Arg51Gly missense_variant Exon 2 of 19 ENST00000264717.7 NP_001477.2 Q14397A0A0C4DFN2
GCKRXM_011532763.1 linkc.151C>G p.Arg51Gly missense_variant Exon 2 of 13 XP_011531065.1
GCKRXR_001738699.1 linkn.217C>G non_coding_transcript_exon_variant Exon 2 of 13

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GCKRENST00000264717.7 linkc.151C>G p.Arg51Gly missense_variant Exon 2 of 19 1 NM_001486.4 ENSP00000264717.2 A0A0C4DFN2
GCKRENST00000472290.1 linkn.173C>G non_coding_transcript_exon_variant Exon 2 of 11 1
GCKRENST00000453813.1 linkc.67C>G p.Arg23Gly missense_variant Exon 1 of 8 3 ENSP00000399463.1 H7C1B4
GCKRENST00000417872.5 linkn.208C>G non_coding_transcript_exon_variant Exon 2 of 7 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251488
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461862
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
15
DANN
Benign
0.95
DEOGEN2
Benign
0.38
T;T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.035
N
LIST_S2
Benign
0.62
T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.67
T
PrimateAI
Benign
0.20
T
PROVEAN
Uncertain
-4.2
D;D
REVEL
Uncertain
0.54
Sift
Benign
0.071
T;D
Sift4G
Benign
0.077
T;D
Vest4
0.71
MutPred
0.46
Loss of solvent accessibility (P = 0.0329);.;
MPC
0.071
ClinPred
0.60
D
GERP RS
-1.3
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375836361; hg19: chr2-27720201; API