Variant 10-69292327-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_001322365.2(HK1):c.97C>T(p.Pro33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 437,766 control chromosomes in the GnomAD database, including 47,170 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14259 hom., cov: 32)

Exomes 𝑓: 0.47 ( 32911 hom. )

Consequence

HK1
NM_001322365.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in the HK1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 13 curated pathogenic missense variants (we use a threshold of 10). The gene has 22 curated benign missense variants. Trascript score misZ: 5.1108 (above the threshold of 3.09). GenCC associations: The gene is linked to retinitis pigmentosa 79, non-spherocytic hemolytic anemia due to hexokinase deficiency, neurodevelopmental disorder with visual defects and brain anomalies, Charcot-Marie-Tooth disease type 4G.

BP4

Computational evidence support a benign effect (MetaRNN=9.723563E-6).

BP6

Variant 10-69292327-C-T is Benign according to our data. Variant chr10-69292327-C-T is described in ClinVar as [Benign]. Clinvar id is 993784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-69292327-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK1	NM_001358263.1 link	c.28-3306C>T		intron_variant	Intron 3 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.28-3306C>T		intron_variant	Intron 3 of 20		NM_001358263.1	ENSP00000494664.1		P19367-3

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61737

AN:

151886

Hom.:

14256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.631

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.485

AC:

54452

AN:

112302

Hom.:

14160

AF XY:

0.475

AC XY:

29328

AN XY:

61704

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.641

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.589

Gnomad SAS exome

AF:

0.410

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.465

Gnomad OTH exome

AF:

0.490

GnomAD4 exome

AF:

0.470

AC:

134282

AN:

285762

Hom.:

32911

Cov.:

AF XY:

0.463

AC XY:

75463

AN XY:

163124

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.641

Gnomad4 ASJ exome

AF:

0.481

Gnomad4 EAS exome

AF:

0.607

Gnomad4 SAS exome

AF:

0.415

Gnomad4 FIN exome

AF:

0.469

Gnomad4 NFE exome

AF:

0.470

Gnomad4 OTH exome

AF:

0.477

GnomAD4 genome

AF:

0.406

AC:

61739

AN:

152004

Hom.:

14259

Cov.:

AF XY:

0.411

AC XY:

30560

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.564

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.632

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.474

Gnomad4 OTH

AF:

0.446

Alfa

AF:

0.435

Hom.:

2878

Bravo

AF:

0.408

TwinsUK

AF:

0.488

AC:

1811

ALSPAC

AF:

0.471

AC:

1816

ExAC

AF:

0.364

AC:

5102

Asia WGS

AF:

0.526

AC:

1828

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 01, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 28, 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

-0.95

CADD

Benign

0.95

DANN

Benign

0.44

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0000097

MetaSVM

Benign

-0.97

GERP RS

-1.5

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