10-69295696-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001358263.1(HK1):c.75+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,526,964 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (5 hom.)
• Consequence: HK1 NM_001358263.1 intron
• Clinical Significance: Benign/Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.243

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-69295696-T-C is Benign according to our data. Variant chr10-69295696-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1284703.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-69295696-T-C is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HK1	NM_001358263.1	c.75+16T>C		intron_variant		ENST00000643399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HK1	ENST00000643399.2	c.75+16T>C		intron_variant			NM_001358263.1

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 214 AN: 152214 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00180 AC: 451 AN: 250472 Hom.: 1 AF XY: 0.00168 AC XY: 228 AN XY: 135458

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00821

Gnomad NFE exome AF: 0.00231

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00136 AC: 1866 AN: 1374750 Hom.: 5 Cov.: 24 AF XY: 0.00137 AC XY: 942 AN XY: 689270

Gnomad4 AFR exome AF: 0.000189

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.0000390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00865

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.00127

GnomAD4 genome AF: 0.00141 AC: 214 AN: 152214 Hom.: 2 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74350

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00631

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00325 Hom.: 1

Bravo AF: 0.000748

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

-

- -

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.8
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs372162023; hg19: chr10-71055452;