Variant 10-69300865-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033500.2(HK1):c.27+4C>T variant causes a splice region, 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. 2/2 splice prediction tools predict no significant impact on normal splicing. 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_033500.2 splice_region, intron

Scores

Splicing: ADA: 0.00001420

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.07

Variant links:

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]

HK1 links:

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

RPS15AP28 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
HK1	NM_001358263.1 link	c.75+5185C>T		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 link	c.75+5185C>T		intron_variant	Intron 4 of 20		NM_001358263.1	ENSP00000494664.1		P19367-3

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15478

AN:

151924

Hom.:

1289

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0724

AC XY:

47543

AN XY:

657076

show subpopulations

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.:

AF XY:

0.106

AC XY:

7842

AN XY:

74318

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over