dbSNP rs691141: HK3:c.-26-112C>T (chr5-176896297-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.792

Publications

17 publications found

Variant links:

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]

HK3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
HK3	NM_002115.3 link	c.-26-112C>T	intron_variant	Intron 1 of 18	ENST00000292432.10	NP_002106.2	P52790A0A024R7R1
HK3	XM_047417134.1 link	c.-26-112C>T	intron_variant	Intron 1 of 17		XP_047273090.1
HK3	XM_011534540.3 link	c.-26-112C>T	intron_variant	Intron 1 of 13		XP_011532842.1
HK3	XR_941102.3 link	n.81-112C>T	intron_variant	Intron 1 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK3	ENST00000292432.10 link	c.-26-112C>T		intron_variant	Intron 1 of 18	1	NM_002115.3	ENSP00000292432.5		P52790

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65764

AN:

151860

Hom.:

14418

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.424

AC:

3624

AN:

8540

American (AMR)

AF:

0.335

AC:

3651

AN:

10910

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

4459

AN:

10782

East Asian (EAS)

AF:

0.431

AC:

10324

AN:

23980

South Asian (SAS)

AF:

0.343

AC:

8290

AN:

24200

European-Finnish (FIN)

AF:

0.477

AC:

17929

AN:

37558

Middle Eastern (MID)

AF:

0.402

AC:

841

AN:

2090

European-Non Finnish (NFE)

AF:

0.454

AC:

97490

AN:

214508

Other (OTH)

AF:

0.424

AC:

8640

AN:

20380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3983

7966

11948

15931

19914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

658

1316

1974

2632

3290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.433

AC:

65801

AN:

151980

Hom.:

14426

Cov.:

AF XY:

0.433

AC XY:

32157

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.432

AC:

17894

AN:

41452

American (AMR)

AF:

0.339

AC:

5176

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

1437

AN:

3464

East Asian (EAS)

AF:

0.420

AC:

2161

AN:

5150

South Asian (SAS)

AF:

0.364

AC:

1754

AN:

4814

European-Finnish (FIN)

AF:

0.473

AC:

4990

AN:

10548

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.455

AC:

30916

AN:

67954

Other (OTH)

AF:

0.406

AC:

855

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1884

3767

5651

7534

9418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.431

Hom.:

13163

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

(source)

DANN

Benign

0.68

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over