rs748235

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000188.3(HK1):c.1443G>A(p.Lys481Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,613,684 control chromosomes in the GnomAD database, including 505,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49185 hom., cov: 32)

Exomes 𝑓: 0.79 ( 455844 hom. )

Consequence

HK1
NM_000188.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.894

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 10-69382664-G-A is Benign according to our data. Variant chr10-69382664-G-A is described in ClinVar as [Benign]. Clinvar id is 255483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-69382664-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.894 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK1	NM_001358263.1 link	c.1455G>A	p.Lys485Lys	synonymous_variant	Exon 13 of 21	ENST00000643399.2	NP_001345192.1
HK1	NM_000188.3 link	c.1443G>A	p.Lys481Lys	synonymous_variant	Exon 10 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.1455G>A	p.Lys485Lys	synonymous_variant	Exon 13 of 21		NM_001358263.1	ENSP00000494664.1		P19367-3
HK1	ENST00000359426.7 link	c.1443G>A	p.Lys481Lys	synonymous_variant	Exon 10 of 18	1	NM_000188.3	ENSP00000352398.6		P19367-1

Frequencies

GnomAD3 genomes

AF:

0.800

AC:

121654

AN:

152012

Hom.:

49144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.880

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.834

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.883

Gnomad FIN

AF:

0.805

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.785

Gnomad OTH

AF:

0.788

GnomAD2 exomes

AF:

0.772

AC:

193253

AN:

250250

AF XY:

0.784

show subpopulations

Gnomad AFR exome

AF:

0.885

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.834

Gnomad EAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.799

Gnomad NFE exome

AF:

0.790

Gnomad OTH exome

AF:

0.763

GnomAD4 exome

AF:

0.787

AC:

1150645

AN:

1461554

Hom.:

455844

Cov.:

AF XY:

0.791

AC XY:

575295

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.891

AC:

29826

AN:

33480

Gnomad4 AMR exome

AF:

0.582

AC:

25964

AN:

44620

Gnomad4 ASJ exome

AF:

0.834

AC:

21757

AN:

26092

Gnomad4 EAS exome

AF:

0.581

AC:

23056

AN:

39694

Gnomad4 SAS exome

AF:

0.890

AC:

76721

AN:

86214

Gnomad4 FIN exome

AF:

0.795

AC:

42474

AN:

53408

Gnomad4 NFE exome

AF:

0.790

AC:

877987

AN:

1111894

Gnomad4 Remaining exome

AF:

0.796

AC:

48081

AN:

60384

Heterozygous variant carriers

15257

30515

45772

61030

76287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

20666

41332

61998

82664

103330

<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:

0.800

AC:

121755

AN:

152130

Hom.:

49185

Cov.:

AF XY:

0.798

AC XY:

59392

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.880

AC:

0.879529

AN:

0.879529

Gnomad4 AMR

AF:

0.663

AC:

0.662503

AN:

0.662503

Gnomad4 ASJ

AF:

0.834

AC:

0.834389

AN:

0.834389

Gnomad4 EAS

AF:

0.647

AC:

0.646887

AN:

0.646887

Gnomad4 SAS

AF:

0.884

AC:

0.88428

AN:

0.88428

Gnomad4 FIN

AF:

0.805

AC:

0.805115

AN:

0.805115

Gnomad4 NFE

AF:

0.785

AC:

0.785048

AN:

0.785048

Gnomad4 OTH

AF:

0.791

AC:

0.79072

AN:

0.79072

Heterozygous variant carriers

1232

2465

3697

4930

6162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<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:

0.789

Hom.:

151717

Bravo

AF:

0.791

Asia WGS

AF:

0.780

AC:

2712

AN:

3478

EpiCase

AF:

0.788

EpiControl

AF:

0.795

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over