10-69295692-AT-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001358263.1(HK1):c.75+23del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00613 in 1,422,050 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (10 hom.)
• Consequence: HK1 NM_001358263.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.177

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 10-69295692-AT-A is Benign according to our data. Variant chr10-69295692-AT-A is described in ClinVar as [Benign]. Clinvar id is 811676.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-69295692-AT-A is described in Lovd as [Benign]. Variant chr10-69295692-AT-A is described in Lovd as [Benign]. Variant chr10-69295692-AT-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK1	NM_001358263.1	c.75+23del		intron_variant		ENST00000643399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK1	ENST00000643399.2	c.75+23del		intron_variant			NM_001358263.1

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 278 AN: 150756 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00126

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000776

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.00126

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.00664 AC: 8443 AN: 1271186 Hom.: 10 Cov.: 23 AF XY: 0.00631 AC XY: 4016 AN XY: 636020

Gnomad4 AFR exome AF: 0.00646

Gnomad4 AMR exome AF: 0.00275

Gnomad4 ASJ exome AF: 0.00163

Gnomad4 EAS exome AF: 0.000810

Gnomad4 SAS exome AF: 0.00358

Gnomad4 FIN exome AF: 0.00384

Gnomad4 NFE exome AF: 0.00761

Gnomad4 OTH exome AF: 0.00572

GnomAD4 genome AF: 0.00186 AC: 281 AN: 150864 Hom.: 1 Cov.: 33 AF XY: 0.00176 AC XY: 130 AN XY: 73718

Gnomad4 AFR AF: 0.00155

Gnomad4 AMR AF: 0.00126

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000778

Gnomad4 SAS AF: 0.00168

Gnomad4 FIN AF: 0.00126

Gnomad4 NFE AF: 0.00251

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.00944 Hom.: 1

Bravo AF: 0.00172

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, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Mar 06, 2019	- -

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111682217; hg19: chr10-71055448;