rs2305198

Positions:

• chr10-69369119-T-C
• chr10-69369119-T-G

Variant summary

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

The ENST00000359426.7(HK1):​c.592-118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 746,636 control chromosomes in the GnomAD database, including 63,615 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 0.45 (16868 hom., cov: 32)
  • Exomes 𝑓: 0.39 (46747 hom.)
• Consequence: HK1 ENST00000359426.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK1	NM_000188.3	c.592-118T>C		intron_variant		ENST00000359426.7	NP_000179.2
HK1	NM_001358263.1	c.604-118T>C		intron_variant		ENST00000643399.2	NP_001345192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000359426.7	c.592-118T>C		intron_variant		1	NM_000188.3	ENSP00000352398	P1
HK1	ENST00000643399.2	c.604-118T>C		intron_variant			NM_001358263.1	ENSP00000494664

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68097 AN: 152004 Hom.: 16829 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.388 AC: 230912 AN: 594514 Hom.: 46747 AF XY: 0.394 AC XY: 126148 AN XY: 319792

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.435

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.383

GnomAD4 genome AF: 0.448 AC: 68187 AN: 152122 Hom.: 16868 Cov.: 32 AF XY: 0.449 AC XY: 33367 AN XY: 74340

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.391

Alfa AF: 0.376 Hom.: 22298

Bravo AF: 0.440

Asia WGS AF: 0.423 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.7
DANN	Benign	0.60

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: rs2305198; hg19: chr10-71128875; COSMIC: COSV53867958; COSMIC: COSV53867958;