10-69300865-C-T

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+5185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 1,458,266 control chromosomes in the GnomAD database, including 8,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1295 hom., cov: 33)
  • Exomes 𝑓: 0.074 (7680 hom.)
• Consequence: HK1 NM_001358263.1 intron
• Scores: Splicing: ADA: 0.00001420
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.07

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]

RPS15AP28 (HGNC:36381): (ribosomal protein S15a pseudogene 28)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BP6: Variant 10-69300865-C-T is Benign according to our data. Variant chr10-69300865-C-T is described in ClinVar as [Benign]. Clinvar id is 994066.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-69300865-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK1	NM_001358263.1	c.75+5185C>T		intron_variant		ENST00000643399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK1	ENST00000643399.2	c.75+5185C>T		intron_variant			NM_001358263.1
RPS15AP28	ENST00000435088.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15478 AN: 151924 Hom.: 1289 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.114 AC: 26982 AN: 237364 Hom.: 3132 AF XY: 0.105 AC XY: 13513 AN XY: 128232

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.492

Gnomad SAS exome AF: 0.0677

Gnomad FIN exome AF: 0.0867

Gnomad NFE exome AF: 0.0518

Gnomad OTH exome AF: 0.0937

GnomAD4 exome AF: 0.0737 AC: 96327 AN: 1306224 Hom.: 7680 Cov.: 19 AF XY: 0.0724 AC XY: 47543 AN XY: 657076

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.0674

Gnomad4 FIN exome AF: 0.0846

Gnomad4 NFE exome AF: 0.0499

Gnomad4 OTH exome AF: 0.0912

GnomAD4 genome AF: 0.102 AC: 15496 AN: 152042 Hom.: 1295 Cov.: 33 AF XY: 0.106 AC XY: 7842 AN XY: 74318

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.0849

Gnomad4 FIN AF: 0.0938

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0577 Hom.: 191

Bravo AF: 0.108

Asia WGS AF: 0.290 AC: 1006 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 28, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	1.1
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs1108272; hg19: chr10-71060621;