Variant 10-69295703-T-C 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_001358263.1(HK1):c.75+23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,446,312 control chromosomes in the GnomAD database, including 361,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38065 hom., cov: 31)

Exomes 𝑓: 0.71 ( 323493 hom. )

Consequence

HK1
NM_001358263.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.701

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:

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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=-0.83).

BP6

Variant 10-69295703-T-C is Benign according to our data. Variant chr10-69295703-T-C is described in ClinVar as [Benign]. Clinvar id is 1285347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK1	NM_001358263.1 linkuse as main transcript	c.75+23T>C		intron_variant		ENST00000643399.2	NP_001345192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK1	ENST00000643399.2 linkuse as main transcript	c.75+23T>C		intron_variant			NM_001358263.1	ENSP00000494664		P19367-3

Frequencies

GnomAD3 genomes

AF:

0.707

AC:

107123

AN:

151612

Hom.:

38046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.733

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.839

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.720

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.740

Gnomad OTH

AF:

0.708

GnomAD3 exomes

AF:

0.698

AC:

169689

AN:

243094

Hom.:

59849

AF XY:

0.704

AC XY:

92459

AN XY:

131396

show subpopulations

Gnomad AFR exome

AF:

0.659

Gnomad AMR exome

AF:

0.525

Gnomad ASJ exome

AF:

0.710

Gnomad EAS exome

AF:

0.830

Gnomad SAS exome

AF:

0.696

Gnomad FIN exome

AF:

0.722

Gnomad NFE exome

AF:

0.731

Gnomad OTH exome

AF:

0.694

GnomAD4 exome

AF:

0.709

AC:

918131

AN:

1294584

Hom.:

323493

Cov.:

AF XY:

0.711

AC XY:

463606

AN XY:

652334

show subpopulations

Gnomad4 AFR exome

AF:

0.651

Gnomad4 AMR exome

AF:

0.537

Gnomad4 ASJ exome

AF:

0.704

Gnomad4 EAS exome

AF:

0.850

Gnomad4 SAS exome

AF:

0.696

Gnomad4 FIN exome

AF:

0.722

Gnomad4 NFE exome

AF:

0.715

Gnomad4 OTH exome

AF:

0.706

GnomAD4 genome

AF:

0.706

AC:

107180

AN:

151728

Hom.:

38065

Cov.:

AF XY:

0.702

AC XY:

52043

AN XY:

74122

show subpopulations

Gnomad4 AFR

AF:

0.665

Gnomad4 AMR

AF:

0.608

Gnomad4 ASJ

AF:

0.718

Gnomad4 EAS

AF:

0.839

Gnomad4 SAS

AF:

0.718

Gnomad4 FIN

AF:

0.720

Gnomad4 NFE

AF:

0.740

Gnomad4 OTH

AF:

0.704

Alfa

AF:

0.673

Hom.:

4344

Bravo

AF:

0.692

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinitis pigmentosa 79

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Hemolytic anemia due to hexokinase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Neurodevelopmental disorder with visual defects and brain anomalies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Charcot-Marie-Tooth disease type 4G

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.7

DANN

Benign

0.88

Splicing

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