Genetic Variant HKDC1:p.Asn917Lys (chr10-69266754-C-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_025130.4(HKDC1):c.2751C>A(p.Asn917Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,609,906 control chromosomes in the GnomAD database, including 93,669 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7786 hom., cov: 32)

Exomes 𝑓: 0.34 ( 85883 hom. )

Consequence

HKDC1
NM_025130.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

35 publications found

Variant links:

Genes affected

HKDC1 (HGNC:23302): (hexokinase domain containing 1) This gene encodes a member of the hexokinase protein family. The encoded protein is involved in glucose metabolism, and reduced expression may be associated with gestational diabetes mellitus. High expression of this gene may also be associated with poor prognosis in hepatocarcinoma. [provided by RefSeq, Sep 2016]

HKDC1 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: G2P

HKDC1 links:

ENSG00000231748 (HGNC:):

ENSG00000231748 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 (MetaRNN=1.6474724E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HKDC1	NM_025130.4 link	c.2751C>A	p.Asn917Lys	missense_variant	Exon 18 of 18	ENST00000354624.6	NP_079406.4	Q2TB90-1B3KT70
HKDC1	XM_047425784.1 link	c.2175C>A	p.Asn725Lys	missense_variant	Exon 15 of 15		XP_047281740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6 link	c.2751C>A	p.Asn917Lys	missense_variant	Exon 18 of 18	1	NM_025130.4	ENSP00000346643.5		Q2TB90-1
ENSG00000231748	ENST00000413220.1 link	n.49-1027G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45640

AN:

151934

Hom.:

7784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.338

GnomAD2 exomes

AF:

0.353

AC:

87383

AN:

247438

AF XY:

0.347

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.500

Gnomad ASJ exome

AF:

0.379

Gnomad EAS exome

AF:

0.536

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.339

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.336

AC:

490135

AN:

1457854

Hom.:

85883

Cov.:

AF XY:

0.334

AC XY:

241932

AN XY:

725106

show subpopulations

African (AFR)

AF:

0.143

AC:

4770

AN:

33292

American (AMR)

AF:

0.491

AC:

21497

AN:

43768

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

9955

AN:

25960

East Asian (EAS)

AF:

0.586

AC:

23204

AN:

39628

South Asian (SAS)

AF:

0.255

AC:

21763

AN:

85296

European-Finnish (FIN)

AF:

0.318

AC:

16967

AN:

53354

Middle Eastern (MID)

AF:

0.385

AC:

2216

AN:

5750

European-Non Finnish (NFE)

AF:

0.332

AC:

368310

AN:

1110564

Other (OTH)

AF:

0.356

AC:

21453

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

14442

28885

43327

57770

72212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11938

23876

35814

47752

59690

<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:

0.300

AC:

45655

AN:

152052

Hom.:

7786

Cov.:

AF XY:

0.303

AC XY:

22529

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.150

AC:

6235

AN:

41496

American (AMR)

AF:

0.429

AC:

6553

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1313

AN:

3472

East Asian (EAS)

AF:

0.570

AC:

2933

AN:

5146

South Asian (SAS)

AF:

0.261

AC:

1257

AN:

4814

European-Finnish (FIN)

AF:

0.324

AC:

3425

AN:

10568

Middle Eastern (MID)

AF:

0.380

AC:

111

AN:

292

European-Non Finnish (NFE)

AF:

0.335

AC:

22800

AN:

67970

Other (OTH)

AF:

0.337

AC:

711

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1574

3148

4721

6295

7869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.334

Hom.:

42980

Bravo

AF:

0.306

TwinsUK

AF:

0.347

AC:

1285

ALSPAC

AF:

0.327

AC:

1262

ESP6500AA

AF:

0.156

AC:

687

ESP6500EA

AF:

0.353

AC:

3039

ExAC

AF:

0.341

AC:

41370

Asia WGS

AF:

0.422

AC:

1466

AN:

3478

EpiCase

AF:

0.356

EpiControl

AF:

0.361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.50

MetaRNN

Benign

0.00016

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.20

PhyloP100

1.2

PrimateAI

Benign

0.38

PROVEAN

Benign

0.11

REVEL

Benign

0.24

Sift

Uncertain

0.017

Sift4G

Uncertain

0.041

Polyphen

0.0

Vest4

0.059

MutPred

0.14

Gain of MoRF binding (P = 0.0366);

MPC

0.16

ClinPred

0.0067

GERP RS

0.70

Varity_R

0.11

gMVP

0.43

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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