rs9645501

chr10-69227010-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.64-197G>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

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=-0.9).
• 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/exons	MANE	UniProt
HKDC1	NM_025130.4	c.64-197G>A		intron_variant		ENST00000354624.6
LOC101928994	NR_120648.1	n.121-1024C>T		intron_variant, non_coding_transcript_variant
HKDC1	XM_011540195.3	c.64-197G>A		intron_variant
HKDC1	XR_007061989.1	n.168-197G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HKDC1	ENST00000354624.6	c.64-197G>A		intron_variant		1	NM_025130.4	P1
	ENST00000450995.1	n.121-1024C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.413

Alfa AF: 0.502 Hom.: 2589

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

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: rs9645501; hg19: chr10-70986766;