chr10-69248900-A-G

Position:

• chr10-69248900-A-G

Variant summary

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

The NM_025130.4(HKDC1):​c.1570+172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 628,408 control chromosomes in the GnomAD database, including 19,825 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 0.20 (3972 hom., cov: 33)
  • Exomes 𝑓: 0.25 (15853 hom.)
• Consequence: HKDC1 NM_025130.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HKDC1	NM_025130.4	c.1570+172A>G		intron_variant		ENST00000354624.6	NP_079406.4
HKDC1	XM_011540195.3	c.1570+172A>G		intron_variant			XP_011538497.1
HKDC1	XM_047425784.1	c.994+172A>G		intron_variant			XP_047281740.1
HKDC1	XR_007061989.1	n.1674+172A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6	c.1570+172A>G		intron_variant		1	NM_025130.4	ENSP00000346643.5
HKDC1	ENST00000488706.1	n.561A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30448 AN: 152132 Hom.: 3969 Cov.: 33

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.251 AC: 119317 AN: 476158 Hom.: 15853 Cov.: 6 AF XY: 0.251 AC XY: 61614 AN XY: 245878

Gnomad4 AFR exome AF: 0.0493

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.200 AC: 30447 AN: 152250 Hom.: 3972 Cov.: 33 AF XY: 0.203 AC XY: 15104 AN XY: 74440

Gnomad4 AFR AF: 0.0524

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.0958

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.185

Alfa AF: 0.249 Hom.: 6519

Bravo AF: 0.181

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.70

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: rs2279927; hg19: chr10-71008656;