rs34380942

chr7-44183693-T-TA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000162.5(GCK):c.45+5215_45+5216insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0659 in 152,098 control chromosomes in the GnomAD database, including 350 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.066 (350 hom., cov: 31)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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]

LOC105375257 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_000162.5	c.45+5215_45+5216insT		intron_variant		ENST00000403799.8
LOC105375257	XR_927221.3	n.240+233_240+234insA		intron_variant, non_coding_transcript_variant
GCK	NM_001354800.1	c.45+5215_45+5216insT		intron_variant
LOC105375257	XR_927222.3	n.918+233_918+234insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000403799.8	c.45+5215_45+5216insT		intron_variant		1	NM_000162.5	P1

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10014 AN: 151980 Hom.: 348 Cov.: 31

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.0858

Gnomad SAS AF: 0.0689

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0659 AC: 10022 AN: 152098 Hom.: 350 Cov.: 31 AF XY: 0.0656 AC XY: 4876 AN XY: 74362

Gnomad4 AFR AF: 0.0561

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.0856

Gnomad4 SAS AF: 0.0689

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.0717

Gnomad4 OTH AF: 0.0711

Alfa AF: 0.0659 Hom.: 41

Asia WGS AF: 0.0720 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34380942; hg19: chr7-44223292;