10-69225511-G-C

Position:

• chr10-69225511-G-C

Variant summary

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

The ENST00000354624.6(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 ENST00000354624.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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=-0.91).
• 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/exons	MANE	Protein	UniProt
HKDC1	NM_025130.4	c.64-1696G>C		intron_variant		ENST00000354624.6	NP_079406.4
LOC101928994	NR_120648.1	n.285+311C>G		intron_variant, non_coding_transcript_variant
HKDC1	XM_011540195.3	c.64-1696G>C		intron_variant			XP_011538497.1
HKDC1	XR_007061989.1	n.168-1696G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6	c.64-1696G>C		intron_variant		1	NM_025130.4	ENSP00000346643	P1
	ENST00000450995.1	n.285+311C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.547

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

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: rs2394529; hg19: chr10-70985267;