rs691141

chr5-176896297-G-Achr5-176896297-G-T

Variant summary

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

The NM_002115.3(HK3):c.-26-112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 504,928 control chromosomes in the GnomAD database, including 49,325 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 0.43 (14426 hom., cov: 32)
  • Exomes 𝑓: 0.44 (34899 hom.)
• Consequence: HK3 NM_002115.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK3	NM_002115.3	c.-26-112C>T		intron_variant		ENST00000292432.10
HK3	XM_011534540.3	c.-26-112C>T		intron_variant
HK3	XM_047417134.1	c.-26-112C>T		intron_variant
HK3	XR_941102.3	n.81-112C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK3	ENST00000292432.10	c.-26-112C>T		intron_variant		1	NM_002115.3	P1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65764 AN: 151860 Hom.: 14418 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.440 AC: 155248 AN: 352948 Hom.: 34899 AF XY: 0.436 AC XY: 79916 AN XY: 183278

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.433 AC: 65801 AN: 151980 Hom.: 14426 Cov.: 32 AF XY: 0.433 AC XY: 32157 AN XY: 74286

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.406

Alfa AF: 0.426 Hom.: 8241

Bravo AF: 0.423

Asia WGS AF: 0.421 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.49
Dann	Benign	0.68

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: rs691141; hg19: chr5-176323298; COSMIC: COSV52838717; COSMIC: COSV52838717;