10-69300878-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001358263.1(HK1):c.75+5198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 1,335,008 control chromosomes in the GnomAD database, including 556,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (61848 hom., cov: 31)
  • Exomes 𝑓: 0.91 (494200 hom.)
• Consequence: HK1 NM_001358263.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -2.27

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 10-69300878-G-A is Benign according to our data. Variant chr10-69300878-G-A is described in ClinVar as [Benign]. Clinvar id is 994063.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-69300878-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK1	NM_001358263.1	c.75+5198G>A		intron_variant		ENST00000643399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK1	ENST00000643399.2	c.75+5198G>A		intron_variant			NM_001358263.1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 136922 AN: 152040 Hom.: 61798 Cov.: 31

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.902

GnomAD3 exomes AF: 0.910 AC: 206473 AN: 226846 Hom.: 94166 AF XY: 0.911 AC XY: 111498 AN XY: 122424

Gnomad AFR exome AF: 0.846

Gnomad AMR exome AF: 0.880

Gnomad ASJ exome AF: 0.846

Gnomad EAS exome AF: 0.991

Gnomad SAS exome AF: 0.884

Gnomad FIN exome AF: 0.944

Gnomad NFE exome AF: 0.922

Gnomad OTH exome AF: 0.906

GnomAD4 exome AF: 0.914 AC: 1080783 AN: 1182850 Hom.: 494200 Cov.: 15 AF XY: 0.913 AC XY: 548232 AN XY: 600408

Gnomad4 AFR exome AF: 0.837

Gnomad4 AMR exome AF: 0.883

Gnomad4 ASJ exome AF: 0.845

Gnomad4 EAS exome AF: 0.994

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.939

Gnomad4 NFE exome AF: 0.918

Gnomad4 OTH exome AF: 0.909

GnomAD4 genome AF: 0.901 AC: 137029 AN: 152158 Hom.: 61848 Cov.: 31 AF XY: 0.901 AC XY: 67014 AN XY: 74374

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.904

Alfa AF: 0.898 Hom.: 11399

Bravo AF: 0.894

Asia WGS AF: 0.939 AC: 3263 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs906221; hg19: chr10-71060634; COSMIC: COSV64354062; COSMIC: COSV64354062;