10-69295692-A-AT

Variant names:

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

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+23dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,444,570 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (3 hom.)
• Consequence: HK1 NM_001358263.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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-A-AT is Benign according to our data. Variant chr10-69295692-A-AT is described in ClinVar as [Benign]. Clinvar id is 3766615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00468 (706/150884) while in subpopulation AFR AF= 0.0137 (563/41180). AF 95% confidence interval is 0.0127. There are 5 homozygotes in gnomad4. There are 349 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK1	NM_001358263.1	c.75+23dupT		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+12_75+13insT		intron_variant	Intron 4 of 20		NM_001358263.1	ENSP00000494664.1

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 691 AN: 150776 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00359

Gnomad ASJ AF: 0.00463

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.000628

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000768

Gnomad OTH AF: 0.00387

GnomAD4 exome AF: 0.00351 AC: 4537 AN: 1293686 Hom.: 3 Cov.: 23 AF XY: 0.00325 AC XY: 2105 AN XY: 647430

Gnomad4 AFR exome AF: 0.0169

Gnomad4 AMR exome AF: 0.00527

Gnomad4 ASJ exome AF: 0.00541

Gnomad4 EAS exome AF: 0.000187

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.000490

Gnomad4 NFE exome AF: 0.00333

Gnomad4 OTH exome AF: 0.00511

GnomAD4 genome AF: 0.00468 AC: 706 AN: 150884 Hom.: 5 Cov.: 33 AF XY: 0.00473 AC XY: 349 AN XY: 73726

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.00463

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.000629

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000769

Gnomad4 OTH AF: 0.00527

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;