rs2278493

Variant names:

• chr5-176887433-C-T
• rs2278493
• NM_002115.3:c.1600+18G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HK3	NM_002115.3	c.1600+18G>A		intron_variant	Intron 11 of 18	ENST00000292432.10	NP_002106.2
HK3	XM_047417134.1	c.1600+18G>A		intron_variant	Intron 11 of 17		XP_047273090.1
HK3	XM_011534540.3	c.1600+18G>A		intron_variant	Intron 11 of 13		XP_011532842.1
HK3	XR_941102.3	n.1706+18G>A		intron_variant	Intron 11 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK3	ENST00000292432.10	c.1600+18G>A		intron_variant	Intron 11 of 18	1	NM_002115.3	ENSP00000292432.5
HK3	ENST00000506834.5	n.612+18G>A		intron_variant	Intron 2 of 9	1
HK3	ENST00000509717.5	n.*74-312G>A		intron_variant	Intron 2 of 2	3		ENSP00000422169.1

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

GnomAD2 exomes AF: 0.362 AC: 90040 AN: 248748 AF XY: 0.360

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 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

African (AFR) AF: 0.109 AC: 3655 AN: 33440

American (AMR) AF: 0.529 AC: 23618 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 8948 AN: 26078

East Asian (EAS) AF: 0.359 AC: 14227 AN: 39654

South Asian (SAS) AF: 0.399 AC: 34400 AN: 86208

European-Finnish (FIN) AF: 0.347 AC: 18380 AN: 52976

Middle Eastern (MID) AF: 0.271 AC: 1556 AN: 5752

European-Non Finnish (NFE) AF: 0.339 AC: 376762 AN: 1110628

Other (OTH) AF: 0.341 AC: 20583 AN: 60310

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

African (AFR) AF: 0.122 AC: 5068 AN: 41540

American (AMR) AF: 0.447 AC: 6842 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3468

East Asian (EAS) AF: 0.392 AC: 2018 AN: 5152

South Asian (SAS) AF: 0.384 AC: 1856 AN: 4832

European-Finnish (FIN) AF: 0.339 AC: 3582 AN: 10574

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22514 AN: 67952

Other (OTH) AF: 0.321 AC: 678 AN: 2110

Alfa AF: 0.328 Hom.: 15028

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
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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