rs9645501

Variant names:

• chr10-69227010-G-A
• rs9645501
• NM_025130.4:c.64-197G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025130.4(HKDC1):​c.64-197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,960 control chromosomes in the GnomAD database, including 16,566 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 0.43 (16566 hom., cov: 31)
• Consequence: HKDC1 NM_025130.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 9 publications found

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

ENSG00000229261 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HKDC1	NM_025130.4	c.64-197G>A		intron_variant	Intron 1 of 17	ENST00000354624.6	NP_079406.4
LOC101928994	NR_120648.1	n.121-1024C>T		intron_variant	Intron 1 of 4
HKDC1	XM_011540195.3	c.64-197G>A		intron_variant	Intron 1 of 15		XP_011538497.1
HKDC1	XR_007061989.1	n.168-197G>A		intron_variant	Intron 1 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6	c.64-197G>A		intron_variant	Intron 1 of 17	1	NM_025130.4	ENSP00000346643.5
ENSG00000229261	ENST00000450995.1	n.121-1024C>T		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64965 AN: 151842 Hom.: 16559 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.416

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.428 AC: 64982 AN: 151960 Hom.: 16566 Cov.: 31 AF XY: 0.428 AC XY: 31788 AN XY: 74256

African (AFR) AF: 0.165 AC: 6845 AN: 41442

American (AMR) AF: 0.403 AC: 6145 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3466

East Asian (EAS) AF: 0.155 AC: 798 AN: 5164

South Asian (SAS) AF: 0.436 AC: 2098 AN: 4810

European-Finnish (FIN) AF: 0.631 AC: 6654 AN: 10542

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39681 AN: 67962

Other (OTH) AF: 0.413 AC: 873 AN: 2114

Alfa AF: 0.473 Hom.: 5607

Bravo AF: 0.395

Asia WGS AF: 0.275 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.026
DANN	Benign	0.44
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9645501; hg19: chr10-70986766; COSMIC: COSV107417904;