rs2268573

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000162.5(GCK):c.483+87A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,601,364 control chromosomes in the GnomAD database, including 208,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). The gene GCK is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.57 ( 25911 hom., cov: 33)

Exomes 𝑓: 0.50 ( 182832 hom. )

Consequence

GCK
NM_000162.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.37

Publications

14 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
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

GCK links:

ENSG00000300758 (HGNC:):

ENSG00000300758 links:

Genome browser will be placed here

ACMG classification

Specifications for GCK are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-44150869-T-G is Benign according to our data. Variant chr7-44150869-T-G is described in ClinVar as Benign. ClinVar VariationId is 676858.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000162.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GCK	NM_000162.5	MANE Select	c.483+87A>C	intron	N/A	NP_000153.1	Q53Y25
GCK	NM_033507.3		c.486+87A>C	intron	N/A	NP_277042.1	P35557-2
GCK	NM_033508.3		c.480+87A>C	intron	N/A	NP_277043.1	P35557-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GCK	ENST00000403799.8	TSL:1 MANE Select	c.483+87A>C	intron	N/A	ENSP00000384247.3	P35557-1
GCK	ENST00000395796.8	TSL:1	n.*481+87A>C	intron	N/A	ENSP00000379142.4	A0A8C8KJG0
GCK	ENST00000671824.1		c.483+87A>C	intron	N/A	ENSP00000500264.1	A0A5F9ZHE0

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

87106

AN:

151982

Hom.:

25887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.493

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.559

GnomAD4 exome

AF:

0.499

AC:

723248

AN:

1449266

Hom.:

182832

AF XY:

0.496

AC XY:

357698

AN XY:

720986

show subpopulations

African (AFR)

AF:

0.745

AC:

24721

AN:

33204

American (AMR)

AF:

0.594

AC:

26288

AN:

44286

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

12870

AN:

25922

East Asian (EAS)

AF:

0.636

AC:

25064

AN:

39414

South Asian (SAS)

AF:

0.430

AC:

36716

AN:

85306

European-Finnish (FIN)

AF:

0.499

AC:

25965

AN:

51982

Middle Eastern (MID)

AF:

0.470

AC:

2397

AN:

5100

European-Non Finnish (NFE)

AF:

0.488

AC:

539104

AN:

1104306

Other (OTH)

AF:

0.504

AC:

30123

AN:

59746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

18962

37925

56887

75850

94812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15954

31908

47862

63816

79770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.573

AC:

87174

AN:

152098

Hom.:

25911

Cov.:

AF XY:

0.572

AC XY:

42507

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.741

AC:

30743

AN:

41492

American (AMR)

AF:

0.568

AC:

8679

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1738

AN:

3468

East Asian (EAS)

AF:

0.633

AC:

3277

AN:

5174

South Asian (SAS)

AF:

0.435

AC:

2099

AN:

4822

European-Finnish (FIN)

AF:

0.493

AC:

5218

AN:

10574

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.495

AC:

33645

AN:

67958

Other (OTH)

AF:

0.558

AC:

1180

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1888

3776

5665

7553

9441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.538

Hom.:

3753

Bravo

AF:

0.589

Asia WGS

AF:

0.524

AC:

1822

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.37

(source)

DANN

Benign

0.43

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over