10-69225907-G-A

Position:

• chr10-69225907-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HKDC1	NM_025130.4	c.64-1300G>A		intron_variant		ENST00000354624.6
LOC101928994	NR_120648.1	n.200C>T		non_coding_transcript_exon_variant	2/5
HKDC1	XM_011540195.3	c.64-1300G>A		intron_variant
HKDC1	XR_007061989.1	n.168-1300G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HKDC1	ENST00000354624.6	c.64-1300G>A		intron_variant		1	NM_025130.4	P1
	ENST00000450995.1	n.200C>T		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14152 AN: 152096 Hom.: 731 Cov.: 32

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: 11 AN: 78 Hom.: 0 Cov.: 0 AF XY: 0.140 AC XY: 7 AN XY: 50

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0930 AC: 14160 AN: 152214 Hom.: 734 Cov.: 32 AF XY: 0.0950 AC XY: 7068 AN XY: 74426

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0860

Gnomad4 OTH AF: 0.0865

Alfa AF: 0.0912 Hom.: 93

Bravo AF: 0.0922

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs5030944; hg19: chr10-70985663;