rs2908277

chr7-44143834-G-Achr7-44143834-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354800.1(GCK):c.*401C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,176 control chromosomes in the GnomAD database, including 2,595 homozygotes. 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: 𝑓 0.17 (2595 hom., cov: 33)
• Consequence: GCK NM_001354800.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_001354800.1	c.*401C>T		3_prime_UTR_variant	11/11
GCK	NM_001354802.1	c.*401C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000673284.1	c.*401C>T		3_prime_UTR_variant	11/11
GCK	ENST00000672743.1	n.784C>T		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26504 AN: 152058 Hom.: 2588 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.160

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.174 AC: 26534 AN: 152176 Hom.: 2595 Cov.: 33 AF XY: 0.176 AC XY: 13079 AN XY: 74374

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.159

Alfa AF: 0.133 Hom.: 2969

Bravo AF: 0.178

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.0
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2908277; hg19: chr7-44183433;