Genetic Variant NM_025130.4:c.*718G>C (chr10-69267475-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_025130.4(HKDC1):c.*718G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 454,846 control chromosomes in the GnomAD database, including 35,653 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 11594 hom., cov: 32)

Exomes 𝑓: 0.39 ( 24059 hom. )

Consequence

HKDC1
NM_025130.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.115

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: G2P

HKDC1 links:

ENSG00000231748 (HGNC:):

ENSG00000231748 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.021).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HKDC1	NM_025130.4 link	c.*718G>C		3_prime_UTR_variant	Exon 18 of 18	ENST00000354624.6	NP_079406.4
HKDC1	XM_047425784.1 link	c.*718G>C		3_prime_UTR_variant	Exon 15 of 15		XP_047281740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6 link	c.*718G>C		3_prime_UTR_variant	Exon 18 of 18	1	NM_025130.4	ENSP00000346643.5
ENSG00000231748	ENST00000413220.1 link	n.48+626C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58548

AN:

151914

Hom.:

11577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.390

GnomAD2 exomes

AF:

0.379

AC:

52529

AN:

138766

AF XY:

0.392

show subpopulations

Gnomad AFR exome

AF:

0.451

Gnomad AMR exome

AF:

0.274

Gnomad ASJ exome

AF:

0.447

Gnomad EAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.375

GnomAD4 exome

AF:

0.389

AC:

117792

AN:

302814

Hom.:

24059

Cov.:

AF XY:

0.403

AC XY:

69517

AN XY:

172482

show subpopulations

African (AFR)

AF:

0.450

AC:

3846

AN:

8538

American (AMR)

AF:

0.274

AC:

7432

AN:

27108

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

4714

AN:

10756

East Asian (EAS)

AF:

0.350

AC:

3208

AN:

9160

South Asian (SAS)

AF:

0.514

AC:

30520

AN:

59394

European-Finnish (FIN)

AF:

0.320

AC:

4103

AN:

12834

Middle Eastern (MID)

AF:

0.442

AC:

1014

AN:

2296

European-Non Finnish (NFE)

AF:

0.363

AC:

57550

AN:

158582

Other (OTH)

AF:

0.382

AC:

5405

AN:

14146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

3546

7092

10638

14184

17730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

406

812

1218

1624

2030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.386

AC:

58611

AN:

152032

Hom.:

11594

Cov.:

AF XY:

0.384

AC XY:

28570

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.456

AC:

18890

AN:

41432

American (AMR)

AF:

0.315

AC:

4811

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1528

AN:

3472

East Asian (EAS)

AF:

0.338

AC:

1754

AN:

5182

South Asian (SAS)

AF:

0.521

AC:

2508

AN:

4812

European-Finnish (FIN)

AF:

0.309

AC:

3261

AN:

10568

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24508

AN:

67982

Other (OTH)

AF:

0.393

AC:

828

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1817

3633

5450

7266

9083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.388

Hom.:

2458

Bravo

AF:

0.384

Asia WGS

AF:

0.408

AC:

1418

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.1

(source)

DANN

Benign

0.78

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over