dbSNP rs4746822: HKDC1:c.63+2687C>T (chr10-69223185-C-T) – 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+2687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,022 control chromosomes in the GnomAD database, including 27,087 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 0.59 ( 27086 hom., cov: 32)

Exomes 𝑓: 0.38 ( 1 hom. )

Consequence

HKDC1
NM_025130.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0290

Publications

23 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 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.63+2687C>T		intron	N/A	NP_079406.4
	LOC101928994	NR_120648.1		n.326G>A		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HKDC1	ENST00000354624.6	TSL:1 MANE Select	c.63+2687C>T	intron	N/A	ENSP00000346643.5	Q2TB90-1
HKDC1	ENST00000953956.1		c.63+2687C>T	intron	N/A	ENSP00000624015.1
HKDC1	ENST00000953957.1		c.63+2687C>T	intron	N/A	ENSP00000624016.1

Frequencies

GnomAD3 genomes

AF:

0.585

AC:

88934

AN:

151896

Hom.:

27052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.556

Gnomad ASJ

AF:

0.443

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.745

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.672

Gnomad OTH

AF:

0.551

GnomAD4 exome

AF:

0.375

AC:

AN:

Hom.:

Cov.:

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:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.586

AC:

89014

AN:

152014

Hom.:

27086

Cov.:

AF XY:

0.585

AC XY:

43492

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.469

AC:

19464

AN:

41466

American (AMR)

AF:

0.556

AC:

8488

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

1537

AN:

3470

East Asian (EAS)

AF:

0.254

AC:

1316

AN:

5174

South Asian (SAS)

AF:

0.579

AC:

2793

AN:

4828

European-Finnish (FIN)

AF:

0.745

AC:

7854

AN:

10542

Middle Eastern (MID)

AF:

0.442

AC:

129

AN:

292

European-Non Finnish (NFE)

AF:

0.672

AC:

45653

AN:

67958

Other (OTH)

AF:

0.544

AC:

1151

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1774

3547

5321

7094

8868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.623

Hom.:

49548

Bravo

AF:

0.561

Asia WGS

AF:

0.407

AC:

1417

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.7

(source)

DANN

Benign

0.56

PhyloP100

-0.029

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