rs2278493

Positions:

• chr5-176887433-C-T

Variant summary

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

The NM_002115.3(HK3):​c.1600+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,611,826 control chromosomes in the GnomAD database, including 95,979 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 (7362 hom., cov: 32)
  • Exomes 𝑓: 0.34 (88617 hom.)
• Consequence: HK3 NM_002115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740

Genes affected

HK3 (HGNC:4925): (hexokinase 3) Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes hexokinase 3. Similar to hexokinases 1 and 2, this allosteric enzyme is inhibited by its product glucose-6-phosphate. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK3	NM_002115.3	c.1600+18G>A		intron_variant		ENST00000292432.10
HK3	XM_011534540.3	c.1600+18G>A		intron_variant
HK3	XM_047417134.1	c.1600+18G>A		intron_variant
HK3	XR_941102.3	n.1706+18G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK3	ENST00000292432.10	c.1600+18G>A		intron_variant		1	NM_002115.3	P1
HK3	ENST00000506834.5	n.612+18G>A		intron_variant, non_coding_transcript_variant		1
HK3	ENST00000509717.5	c.*74-312G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44079 AN: 152006 Hom.: 7360 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.319

GnomAD3 exomes AF: 0.362 AC: 90040 AN: 248748 Hom.: 17670 AF XY: 0.360 AC XY: 48525 AN XY: 134764

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.544

Gnomad ASJ exome AF: 0.344

Gnomad EAS exome AF: 0.398

Gnomad SAS exome AF: 0.402

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.344 AC: 502129 AN: 1459702 Hom.: 88617 Cov.: 41 AF XY: 0.344 AC XY: 250053 AN XY: 725936

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.529

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.359

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.290 AC: 44090 AN: 152124 Hom.: 7362 Cov.: 32 AF XY: 0.292 AC XY: 21747 AN XY: 74368

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.321

Alfa AF: 0.333 Hom.: 12419

Bravo AF: 0.292

Asia WGS AF: 0.347 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.55

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: rs2278493; hg19: chr5-176314434; COSMIC: COSV52837914; COSMIC: COSV52837914;