rs2394538

chr10-69273941-T-C

Variant summary

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

The ENST00000464803.6(HK1):c.-196+2845T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,064 control chromosomes in the GnomAD database, including 7,343 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 0.29 (7343 hom., cov: 32)
• Consequence: HK1 ENST00000464803.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK1	NM_001322364.2	c.-74+3833T>C		intron_variant
HK1	NM_001322365.2	c.-196+2845T>C		intron_variant
HK1	NM_033497.3	c.-196+3833T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK1	ENST00000464803.6	c.-196+2845T>C		intron_variant		1
HK1	ENST00000480047.5	n.109+3833T>C		intron_variant, non_coding_transcript_variant		1
HK1	ENST00000436817.6	c.-196+3833T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43982 AN: 151946 Hom.: 7341 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.289 AC: 43988 AN: 152064 Hom.: 7343 Cov.: 32 AF XY: 0.291 AC XY: 21657 AN XY: 74352

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.330

Alfa AF: 0.312 Hom.: 3649

Bravo AF: 0.296

Asia WGS AF: 0.412 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.5
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2394538; hg19: chr10-71033697;