rs5030917

Positions:

• chr10-69295445-G-T

Variant summary

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

The NM_001358263.1(HK1):​c.28-188G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,256 control chromosomes in the GnomAD database, including 1,838 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 0.13 (1838 hom., cov: 32)
• Consequence: HK1 NM_001358263.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

Genes affected

HK1 (HGNC:4922): (hexokinase 1) Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in several transcript variants which encode different isoforms, some of which are tissue-specific. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK1	NM_001358263.1	c.28-188G>T		intron_variant		ENST00000643399.2	NP_001345192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2	c.28-188G>T		intron_variant			NM_001358263.1	ENSP00000494664

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20454 AN: 152140 Hom.: 1832 Cov.: 32

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0862

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.134 AC: 20463 AN: 152256 Hom.: 1838 Cov.: 32 AF XY: 0.139 AC XY: 10369 AN XY: 74438

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0860

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.144

Alfa AF: 0.147 Hom.: 382

Bravo AF: 0.136

Asia WGS AF: 0.129 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5030917; hg19: chr10-71055201;