rs17476364

chr10-69334748-T-C

Variant summary

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

The NM_001358263.1(HK1):c.76-9079T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 152,186 control chromosomes in the GnomAD database, including 427 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 0.064 (427 hom., cov: 32)
• Consequence: HK1 NM_001358263.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.096 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK1	NM_000188.3	c.64-9079T>C		intron_variant		ENST00000359426.7
HK1	NM_001358263.1	c.76-9079T>C		intron_variant		ENST00000643399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK1	ENST00000359426.7	c.64-9079T>C		intron_variant		1	NM_000188.3	P1
HK1	ENST00000643399.2	c.76-9079T>C		intron_variant			NM_001358263.1

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9713 AN: 152068 Hom.: 429 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.0506

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0638 AC: 9707 AN: 152186 Hom.: 427 Cov.: 32 AF XY: 0.0610 AC XY: 4539 AN XY: 74400

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.0717

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0331

Gnomad4 FIN AF: 0.0506

Gnomad4 NFE AF: 0.0980

Gnomad4 OTH AF: 0.0706

Alfa AF: 0.0736 Hom.: 61

Bravo AF: 0.0645

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.3
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs17476364; hg19: chr10-71094504;