rs906216

Positions:

• chr10-69338439-G-T

Variant summary

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

The NM_000188.3(HK1):​c.64-5388G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,257,506 control chromosomes in the GnomAD database, including 124,332 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 0.46 (17262 hom., cov: 31)
  • Exomes 𝑓: 0.44 (107070 hom.)
• Consequence: HK1 NM_000188.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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]

HK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK1	NM_001358263.1	c.76-5388G>T		intron_variant		ENST00000643399.2	NP_001345192.1
HK1	NM_000188.3	c.64-5388G>T		intron_variant		ENST00000359426.7	NP_000179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2	c.76-5388G>T		intron_variant			NM_001358263.1	ENSP00000494664.1
HK1	ENST00000359426.7	c.64-5388G>T		intron_variant		1	NM_000188.3	ENSP00000352398.6

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69547 AN: 151744 Hom.: 17237 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.435 AC: 480965 AN: 1105646 Hom.: 107070 Cov.: 32 AF XY: 0.433 AC XY: 232751 AN XY: 537300

Gnomad4 AFR exome AF: 0.647

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.378

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.458 AC: 69622 AN: 151860 Hom.: 17262 Cov.: 31 AF XY: 0.453 AC XY: 33577 AN XY: 74202

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.410

Alfa AF: 0.426 Hom.: 29230

Bravo AF: 0.455

Asia WGS AF: 0.281 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.50

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: rs906216; hg19: chr10-71098195;