dbSNP rs2279927: HKDC1:c.1570+172A>G (chr10-69248900-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025130.4(HKDC1):c.1570+172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 628,408 control chromosomes in the GnomAD database, including 19,825 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 0.20 ( 3972 hom., cov: 33)

Exomes 𝑓: 0.25 ( 15853 hom. )

Consequence

HKDC1
NM_025130.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.663

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
HKDC1	NM_025130.4 link	c.1570+172A>G	intron_variant	Intron 10 of 17	ENST00000354624.6	NP_079406.4
HKDC1	XM_011540195.3 link	c.1570+172A>G	intron_variant	Intron 10 of 15		XP_011538497.1
HKDC1	XM_047425784.1 link	c.994+172A>G	intron_variant	Intron 7 of 14		XP_047281740.1
HKDC1	XR_007061989.1 link	n.1674+172A>G	intron_variant	Intron 10 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6 link	c.1570+172A>G		intron_variant	Intron 10 of 17	1	NM_025130.4	ENSP00000346643.5
HKDC1	ENST00000488706.1 link	n.561A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30448

AN:

152132

Hom.:

3969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0526

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0963

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.186

GnomAD4 exome

AF:

0.251

AC:

119317

AN:

476158

Hom.:

15853

Cov.:

AF XY:

0.251

AC XY:

61614

AN XY:

245878

show subpopulations

African (AFR)

AF:

0.0493

AC:

643

AN:

13034

American (AMR)

AF:

0.203

AC:

3018

AN:

14836

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

1960

AN:

13498

East Asian (EAS)

AF:

0.133

AC:

4000

AN:

30154

South Asian (SAS)

AF:

0.233

AC:

8838

AN:

37890

European-Finnish (FIN)

AF:

0.327

AC:

9467

AN:

28954

Middle Eastern (MID)

AF:

0.134

AC:

266

AN:

1984

European-Non Finnish (NFE)

AF:

0.276

AC:

85311

AN:

309354

Other (OTH)

AF:

0.220

AC:

5814

AN:

26454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4397

8794

13192

17589

21986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1074

2148

3222

4296

5370

<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:

0.200

AC:

30447

AN:

152250

Hom.:

3972

Cov.:

AF XY:

0.203

AC XY:

15104

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0524

AC:

2180

AN:

41566

American (AMR)

AF:

0.207

AC:

3163

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

501

AN:

3470

East Asian (EAS)

AF:

0.0958

AC:

497

AN:

5190

South Asian (SAS)

AF:

0.219

AC:

1056

AN:

4822

European-Finnish (FIN)

AF:

0.350

AC:

3706

AN:

10584

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18735

AN:

68002

Other (OTH)

AF:

0.185

AC:

391

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1200

2400

3601

4801

6001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.243

Hom.:

8048

Bravo

AF:

0.181

Asia WGS

AF:

0.139

AC:

486

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.40

(source)

DANN

Benign

0.70

PhyloP100

-0.66

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