10-69340157-T-C

Position:

• chr10-69340157-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358263.1(HK1):​c.76-3670T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,076 control chromosomes in the GnomAD database, including 22,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22901 hom., cov: 33)
• Consequence: HK1 NM_001358263.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK1	NM_000188.3	c.64-3670T>C		intron_variant		ENST00000359426.7
HK1	NM_001358263.1	c.76-3670T>C		intron_variant		ENST00000643399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK1	ENST00000359426.7	c.64-3670T>C		intron_variant		1	NM_000188.3	P1
HK1	ENST00000643399.2	c.76-3670T>C		intron_variant			NM_001358263.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81632 AN: 151958 Hom.: 22873 Cov.: 33

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81707 AN: 152076 Hom.: 22901 Cov.: 33 AF XY: 0.538 AC XY: 40017 AN XY: 74320

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.482

Alfa AF: 0.498 Hom.: 34037

Bravo AF: 0.527

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7072268; hg19: chr10-71099913;