10-69295692-AT-A

Variant names:

• chr10-69295692-AT-A
• rs111682217
• NM_001358263.1:c.75+23delT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001358263.1(HK1):​c.75+23delT 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 Benign. Variant got -10 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].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00186 (281/150864) while in subpopulation NFE AF= 0.00251 (170/67652). AF 95% confidence interval is 0.0022. There are 1 homozygotes in gnomad4. There are 130 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK1	NM_001358263.1	c.75+23delT		intron_variant	Intron 4 of 20	ENST00000643399.2	NP_001345192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2	c.75+13delT		intron_variant	Intron 4 of 20		NM_001358263.1	ENSP00000494664.1

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 provided Benign:2

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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;