rs748235

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001358263.1(HK1):c.1455G>A(p.Lys485=) 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_001358263.1 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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HK1	NM_001358263.1 linkuse as main transcript	c.1455G>A	p.Lys485=	synonymous_variant	13/21	ENST00000643399.2	NP_001345192.1
HK1	NM_000188.3 linkuse as main transcript	c.1443G>A	p.Lys481=	synonymous_variant	10/18	ENST00000359426.7	NP_000179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2 linkuse as main transcript	c.1455G>A	p.Lys485=	synonymous_variant	13/21		NM_001358263.1	ENSP00000494664		P19367-3
HK1	ENST00000359426.7 linkuse as main transcript	c.1443G>A	p.Lys481=	synonymous_variant	10/18	1	NM_000188.3	ENSP00000352398	P1	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

GnomAD3 exomes

AF:

0.772

AC:

193253

AN:

250250

Hom.:

75900

AF XY:

0.784

AC XY:

105983

AN XY:

135262

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 SAS exome

AF:

0.890

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

Gnomad4 AMR exome

AF:

0.582

Gnomad4 ASJ exome

AF:

0.834

Gnomad4 EAS exome

AF:

0.581

Gnomad4 SAS exome

AF:

0.890

Gnomad4 FIN exome

AF:

0.795

Gnomad4 NFE exome

AF:

0.790

Gnomad4 OTH exome

AF:

0.796

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

Gnomad4 AMR

AF:

0.663

Gnomad4 ASJ

AF:

0.834

Gnomad4 EAS

AF:

0.647

Gnomad4 SAS

AF:

0.884

Gnomad4 FIN

AF:

0.805

Gnomad4 NFE

AF:

0.785

Gnomad4 OTH

AF:

0.791

Alfa

AF:

0.786

Hom.:

104859

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinitis pigmentosa 79

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Hemolytic anemia due to hexokinase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Neurodevelopmental disorder with visual defects and brain anomalies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Charcot-Marie-Tooth disease type 4G

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

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

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