Variant 2-27497334-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001486.4(GCKR):c.151C>G(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 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GCKR
NM_001486.4 missense

Scores

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]

GCKR links:

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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
GCKR	NM_001486.4 link	c.151C>G	p.Arg51Gly	missense_variant	Exon 2 of 19	ENST00000264717.7	NP_001477.2	Q14397A0A0C4DFN2
GCKR	XM_011532763.1 link	c.151C>G	p.Arg51Gly	missense_variant	Exon 2 of 13		XP_011531065.1
GCKR	XR_001738699.1 link	n.217C>G		non_coding_transcript_exon_variant	Exon 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GCKR	ENST00000264717.7 link	c.151C>G	p.Arg51Gly	missense_variant	Exon 2 of 19	1	NM_001486.4	ENSP00000264717.2	A0A0C4DFN2
GCKR	ENST00000472290.1 link	n.173C>G		non_coding_transcript_exon_variant	Exon 2 of 11	1
GCKR	ENST00000453813.1 link	c.67C>G	p.Arg23Gly	missense_variant	Exon 1 of 8	3		ENSP00000399463.1	H7C1B4
GCKR	ENST00000417872.5 link	n.208C>G		non_coding_transcript_exon_variant	Exon 2 of 7	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251488

Hom.:

AF XY:

0.00000736

AC XY:

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:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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.:

ExAC

AF:

0.00000824

AC:

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

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.38

T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.67

PrimateAI

Benign

0.20

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over