Variant chr10-69232818-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025130.4(HKDC1):c.281A>C(p.Lys94Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

HKDC1
NM_025130.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

HKDC1 (HGNC:23302): (hexokinase domain containing 1) This gene encodes a member of the hexokinase protein family. The encoded protein is involved in glucose metabolism, and reduced expression may be associated with gestational diabetes mellitus. High expression of this gene may also be associated with poor prognosis in hepatocarcinoma. [provided by RefSeq, Sep 2016]

HKDC1 links:

HKDC1 (HGNC:):

HKDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32463247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HKDC1	NM_025130.4 linkuse as main transcript	c.281A>C	p.Lys94Thr	missense_variant	3/18	ENST00000354624.6	NP_079406.4	Q2TB90-1B3KT70
HKDC1	XM_011540195.3 linkuse as main transcript	c.281A>C	p.Lys94Thr	missense_variant	3/16		XP_011538497.1
HKDC1	XR_007061989.1 linkuse as main transcript	n.385A>C		non_coding_transcript_exon_variant	3/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6 linkuse as main transcript	c.281A>C	p.Lys94Thr	missense_variant	3/18	1	NM_025130.4	ENSP00000346643.5		Q2TB90-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251414

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2022

The c.281A>C (p.K94T) alteration is located in exon 3 (coding exon 3) of the HKDC1 gene. This alteration results from a A to C substitution at nucleotide position 281, causing the lysine (K) at amino acid position 94 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.32

MetaSVM

Uncertain

0.60

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.67

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.71

REVEL

Uncertain

0.39

Sift

Benign

0.19

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.31

MutPred

0.59

Loss of MoRF binding (P = 0.0546);

MVP

0.83

MPC

0.17

ClinPred

0.17

GERP RS

3.1

Varity_R

0.34

gMVP

0.71

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

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