dbSNP rs7089312: HKDC1:c.63+2278G>A (chr10-69222776-G-A) – 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.63+2278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,140 control chromosomes in the GnomAD database, including 4,381 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 0.22 ( 4379 hom., cov: 32)

Exomes 𝑓: 0.40 ( 2 hom. )

Consequence

HKDC1
NM_025130.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.419

Publications

3 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:

ENSG00000229261 (HGNC:):

ENSG00000229261 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HKDC1	NM_025130.4 link	c.63+2278G>A	intron_variant	Intron 1 of 17	ENST00000354624.6	NP_079406.4	Q2TB90-1B3KT70
LOC101928994	NR_120648.1 link	n.493+101C>T	intron_variant	Intron 4 of 4
HKDC1	XM_011540195.3 link	c.63+2278G>A	intron_variant	Intron 1 of 15		XP_011538497.1
HKDC1	XR_007061989.1 link	n.167+2278G>A	intron_variant	Intron 1 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6 link	c.63+2278G>A		intron_variant	Intron 1 of 17	1	NM_025130.4	ENSP00000346643.5		Q2TB90-1
ENSG00000229261	ENST00000450995.1 link	n.493+101C>T		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33055

AN:

152004

Hom.:

4378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0811

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.400

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.217

AC:

33048

AN:

152120

Hom.:

4379

Cov.:

AF XY:

0.215

AC XY:

15952

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0808

AC:

3356

AN:

41514

American (AMR)

AF:

0.232

AC:

3536

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

761

AN:

3470

East Asian (EAS)

AF:

0.0102

AC:

AN:

5182

South Asian (SAS)

AF:

0.265

AC:

1274

AN:

4810

European-Finnish (FIN)

AF:

0.240

AC:

2546

AN:

10594

Middle Eastern (MID)

AF:

0.271

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.305

AC:

20750

AN:

67966

Other (OTH)

AF:

0.219

AC:

463

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1219

2437

3656

4874

6093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.281

Hom.:

2888

Bravo

AF:

0.206

Asia WGS

AF:

0.114

AC:

398

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.2

(source)

DANN

Benign

0.72

PhyloP100

0.42

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