Variant chr7-44144376-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000162.5(GCK):c.*759del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 11659 hom., cov: 0)

Exomes 𝑓: 0.14 ( 3 hom. )

Consequence

GCK
NM_000162.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.01

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-44144376-TG-T is Benign according to our data. Variant chr7-44144376-TG-T is described in ClinVar as [Benign]. Clinvar id is 360286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_000162.5 linkuse as main transcript	c.*759del		3_prime_UTR_variant	10/10	ENST00000403799.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000403799.8 linkuse as main transcript	c.*759del		3_prime_UTR_variant	10/10	1	NM_000162.5	P1	P35557-1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50716

AN:

152070

Hom.:

11624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.653

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.278

GnomAD4 exome

AF:

0.140

AC:

AN:

136

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

Gnomad4 AMR exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.188

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.334

AC:

50794

AN:

152188

Hom.:

11659

Cov.:

AF XY:

0.335

AC XY:

24942

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.653

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.383

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.234

Gnomad4 NFE

AF:

0.179

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.0745

Hom.:

188

Bravo

AF:

0.351

Asia WGS

AF:

0.331

AC:

1149

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Transient Neonatal Diabetes, Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Maturity onset diabetes mellitus in young

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Permanent neonatal diabetes mellitus

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hyperinsulinism, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over