dbSNP rs5030944: HKDC1:c.64-1300G>A (chr10-69225907-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.64-1300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 152,292 control chromosomes in the GnomAD database, including 734 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 0.093 ( 734 hom., cov: 32)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

HKDC1
NM_025130.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0460

Publications

0 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025130.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HKDC1	NM_025130.4	MANE Select	c.64-1300G>A		intron	N/A	NP_079406.4
	LOC101928994	NR_120648.1		n.200C>T		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HKDC1	ENST00000354624.6	TSL:1 MANE Select	c.64-1300G>A	intron	N/A	ENSP00000346643.5	Q2TB90-1
HKDC1	ENST00000953956.1		c.64-1300G>A	intron	N/A	ENSP00000624015.1
HKDC1	ENST00000953957.1		c.64-1300G>A	intron	N/A	ENSP00000624016.1

Frequencies

GnomAD3 genomes

AF:

0.0930

AC:

14152

AN:

152096

Hom.:

731

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0787

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0697

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0860

Gnomad OTH

AF:

0.0879

GnomAD4 exome

AF:

0.141

AC:

AN:

Hom.:

Cov.:

AF XY:

0.140

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.143

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.130

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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:

0.0930

AC:

14160

AN:

152214

Hom.:

734

Cov.:

AF XY:

0.0950

AC XY:

7068

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0787

AC:

3266

AN:

41512

American (AMR)

AF:

0.128

AC:

1961

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0697

AC:

242

AN:

3470

East Asian (EAS)

AF:

0.121

AC:

628

AN:

5176

South Asian (SAS)

AF:

0.139

AC:

669

AN:

4820

European-Finnish (FIN)

AF:

0.113

AC:

1200

AN:

10602

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0860

AC:

5851

AN:

68020

Other (OTH)

AF:

0.0865

AC:

183

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

655

1311

1966

2622

3277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0911

Hom.:

Bravo

AF:

0.0922

Asia WGS

AF:

0.126

AC:

440

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.3

(source)

DANN

Benign

0.62

PhyloP100

0.046

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over