rs5030949

Positions:

• chr10-69278584-C-A
• chr10-69278584-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001358263.1(HK1):​c.-397C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,060 control chromosomes in the GnomAD database, including 6,064 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 0.26 (6062 hom., cov: 32)
  • Exomes 𝑓: 0.41 (2 hom.)
• Consequence: HK1 NM_001358263.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK1	NM_001358263.1	c.-397C>A		5_prime_UTR_variant	1/21	ENST00000643399.2	NP_001345192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2	c.-397C>A		5_prime_UTR_variant	1/21		NM_001358263.1	ENSP00000494664

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39756 AN: 151920 Hom.: 6061 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.409 AC: 9 AN: 22 Hom.: 2 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.262 AC: 39760 AN: 152038 Hom.: 6062 Cov.: 32 AF XY: 0.263 AC XY: 19557 AN XY: 74300

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.306

Alfa AF: 0.297 Hom.: 13756

Bravo AF: 0.273

Asia WGS AF: 0.404 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5030949; hg19: chr10-71038340;