rs11596193

chr10-69348393-G-A

Variant summary

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

The NM_001358263.1(HK1):c.238+4404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,266 control chromosomes in the GnomAD database, including 1,347 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 0.10 (1347 hom., cov: 32)
• Consequence: HK1 NM_001358263.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903

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 = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK1	NM_000188.3	c.226+4404G>A		intron_variant		ENST00000359426.7
HK1	NM_001358263.1	c.238+4404G>A		intron_variant		ENST00000643399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK1	ENST00000359426.7	c.226+4404G>A		intron_variant		1	NM_000188.3	P1
HK1	ENST00000643399.2	c.238+4404G>A		intron_variant			NM_001358263.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15703 AN: 152148 Hom.: 1343 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.0864

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

GnomAD4 genome AF: 0.103 AC: 15725 AN: 152266 Hom.: 1347 Cov.: 32 AF XY: 0.103 AC XY: 7686 AN XY: 74462

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0763 Hom.: 142

Bravo AF: 0.107

Asia WGS AF: 0.0660 AC: 230 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	0.50
Dann	Benign	0.70

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: rs11596193; hg19: chr10-71108149;