Variant chr10-69232865-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025130.4(HKDC1):c.328C>G(p.Gln110Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (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: 1.84

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HKDC1	NM_025130.4 linkuse as main transcript	c.328C>G	p.Gln110Glu	missense_variant	3/18	ENST00000354624.6	NP_079406.4	Q2TB90-1B3KT70
HKDC1	XM_011540195.3 linkuse as main transcript	c.328C>G	p.Gln110Glu	missense_variant	3/16		XP_011538497.1
HKDC1	XR_007061989.1 linkuse as main transcript	n.432C>G		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.328C>G	p.Gln110Glu	missense_variant	3/18	1	NM_025130.4	ENSP00000346643.5		Q2TB90-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461664

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Sep 15, 2021

The c.328C>G (p.Q110E) alteration is located in exon 3 (coding exon 3) of the HKDC1 gene. This alteration results from a C to G substitution at nucleotide position 328, causing the glutamine (Q) at amino acid position 110 to be replaced by a glutamic acid (E). 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

0.080

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.25

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.85

M_CAP

Benign

0.018

MetaRNN

Benign

0.13

MetaSVM

Uncertain

0.17

MutationAssessor

Benign

0.10

MutationTaster

Benign

0.68

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.40

REVEL

Uncertain

0.30

Sift

Benign

0.38

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.13

MutPred

0.33

Gain of disorder (P = 0.0798);

MVP

0.85

MPC

0.15

ClinPred

0.32

GERP RS

4.3

Varity_R

0.25

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.38

Position offset: -3

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