chr10-69225511-G-C

Variant names:

• chr10-69225511-G-C
• rs2394529
• NM_025130.4:c.64-1696G>C

Variant summary

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

The NM_025130.4(HKDC1):​c.64-1696G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,992 control chromosomes in the GnomAD database, including 27,152 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 (27152 hom., cov: 31)
• Consequence: HKDC1 NM_025130.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HKDC1	NM_025130.4	c.64-1696G>C		intron_variant	Intron 1 of 17	ENST00000354624.6	NP_079406.4
LOC101928994	NR_120648.1	n.285+311C>G		intron_variant	Intron 2 of 4
HKDC1	XM_011540195.3	c.64-1696G>C		intron_variant	Intron 1 of 15		XP_011538497.1
HKDC1	XR_007061989.1	n.168-1696G>C		intron_variant	Intron 1 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6	c.64-1696G>C		intron_variant	Intron 1 of 17	1	NM_025130.4	ENSP00000346643.5
ENSG00000229261	ENST00000450995.1	n.285+311C>G		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89125 AN: 151874 Hom.: 27119 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.587 AC: 89202 AN: 151992 Hom.: 27152 Cov.: 31 AF XY: 0.587 AC XY: 43595 AN XY: 74306

African (AFR) AF: 0.471 AC: 19495 AN: 41416

American (AMR) AF: 0.557 AC: 8499 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1442 AN: 5170

South Asian (SAS) AF: 0.579 AC: 2788 AN: 4816

European-Finnish (FIN) AF: 0.744 AC: 7860 AN: 10564

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45663 AN: 67964

Other (OTH) AF: 0.547 AC: 1156 AN: 2112

Alfa AF: 0.542 Hom.: 1745

Bravo AF: 0.563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.0
DANN	Benign	0.58
PhyloP100		0.029
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: rs2394529; hg19: chr10-70985267;