rs1133189

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001358263.1(HK1):c.90C>G(p.Leu30Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,610,334 control chromosomes in the GnomAD database, including 109,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10109 hom., cov: 31)

Exomes 𝑓: 0.36 ( 99778 hom. )

Consequence

HK1
NM_001358263.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.347

Publications

18 publications found

Variant links:

Genes affected

HK1 (HGNC:4922): (hexokinase 1) Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in several transcript variants which encode different isoforms, some of which are tissue-specific. [provided by RefSeq, Apr 2016]

HK1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with visual defects and brain anomalies
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa 79
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
non-spherocytic hemolytic anemia due to hexokinase deficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
Charcot-Marie-Tooth disease type 4G
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

HK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 10-69343841-C-G is Benign according to our data. Variant chr10-69343841-C-G is described in ClinVar as Benign. ClinVar VariationId is 439787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.347 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK1	NM_001358263.1 link	c.90C>G	p.Leu30Leu	synonymous_variant	Exon 5 of 21	ENST00000643399.2	NP_001345192.1
HK1	NM_000188.3 link	c.78C>G	p.Leu26Leu	synonymous_variant	Exon 2 of 18	ENST00000359426.7	NP_000179.2	P19367-1B3KXY9A8K7J7Q59FD4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2 link	c.90C>G	p.Leu30Leu	synonymous_variant	Exon 5 of 21		NM_001358263.1	ENSP00000494664.1		P19367-3
HK1	ENST00000359426.7 link	c.78C>G	p.Leu26Leu	synonymous_variant	Exon 2 of 18	1	NM_000188.3	ENSP00000352398.6		P19367-1

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54245

AN:

151800

Hom.:

10103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.327

GnomAD2 exomes

AF:

0.314

AC:

78903

AN:

251444

AF XY:

0.317

show subpopulations

Gnomad AFR exome

AF:

0.401

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.269

Gnomad EAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.383

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.363

AC:

529833

AN:

1458416

Hom.:

99778

Cov.:

AF XY:

0.361

AC XY:

262098

AN XY:

725694

show subpopulations

African (AFR)

AF:

0.402

AC:

13437

AN:

33422

American (AMR)

AF:

0.175

AC:

7843

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

7199

AN:

26112

East Asian (EAS)

AF:

0.143

AC:

5660

AN:

39692

South Asian (SAS)

AF:

0.274

AC:

23585

AN:

86196

European-Finnish (FIN)

AF:

0.364

AC:

19462

AN:

53404

Middle Eastern (MID)

AF:

0.239

AC:

1372

AN:

5748

European-Non Finnish (NFE)

AF:

0.389

AC:

430955

AN:

1108844

Other (OTH)

AF:

0.337

AC:

20320

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

16698

33396

50093

66791

83489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13254

26508

39762

53016

66270

<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:

0.357

AC:

54285

AN:

151918

Hom.:

10109

Cov.:

AF XY:

0.352

AC XY:

26147

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.403

AC:

16688

AN:

41400

American (AMR)

AF:

0.262

AC:

4005

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

939

AN:

3470

East Asian (EAS)

AF:

0.136

AC:

703

AN:

5158

South Asian (SAS)

AF:

0.267

AC:

1281

AN:

4806

European-Finnish (FIN)

AF:

0.344

AC:

3631

AN:

10556

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.381

AC:

25908

AN:

67956

Other (OTH)

AF:

0.330

AC:

695

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1695

3391

5086

6782

8477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.363

Hom.:

3441

Bravo

AF:

0.351

Asia WGS

AF:

0.234

AC:

814

AN:

3478

EpiCase

AF:

0.367

EpiControl

AF:

0.365

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 79

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hemolytic anemia due to hexokinase deficiency

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neurodevelopmental disorder with visual defects and brain anomalies

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease type 4G

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.6

(source)

DANN

Benign

0.69

PhyloP100

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over