10-69333763-C-G

Position:

• chr10-69333763-C-G

Variant summary

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

The NM_000188.3(HK1):​c.64-10064C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,938 control chromosomes in the GnomAD database, including 4,855 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 0.22 (4855 hom., cov: 31)
• Consequence: HK1 NM_000188.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

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 (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK1	NM_001358263.1	c.76-10064C>G		intron_variant		ENST00000643399.2	NP_001345192.1
HK1	NM_000188.3	c.64-10064C>G		intron_variant		ENST00000359426.7	NP_000179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2	c.76-10064C>G		intron_variant			NM_001358263.1	ENSP00000494664.1
HK1	ENST00000359426.7	c.64-10064C>G		intron_variant		1	NM_000188.3	ENSP00000352398.6

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33357 AN: 151820 Hom.: 4838 Cov.: 31

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.0749

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.220 AC: 33412 AN: 151938 Hom.: 4855 Cov.: 31 AF XY: 0.225 AC XY: 16694 AN XY: 74250

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.178

Alfa AF: 0.170 Hom.: 371

Bravo AF: 0.221

Asia WGS AF: 0.228 AC: 793 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	1.7
DANN	Benign	0.52

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: rs10823345; hg19: chr10-71093519;