rs7089312

Positions:

• chr10-69222776-G-A
• chr10-69222776-G-C

Variant summary

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

The NM_025130.4(HKDC1):​c.63+2278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,140 control chromosomes in the GnomAD database, including 4,381 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 0.22 (4379 hom., cov: 32)
  • Exomes 𝑓: 0.40 (2 hom.)
• Consequence: HKDC1 NM_025130.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HKDC1	NM_025130.4	c.63+2278G>A		intron_variant		ENST00000354624.6	NP_079406.4
LOC101928994	NR_120648.1	n.493+101C>T		intron_variant, non_coding_transcript_variant
HKDC1	XM_011540195.3	c.63+2278G>A		intron_variant			XP_011538497.1
HKDC1	XR_007061989.1	n.167+2278G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6	c.63+2278G>A		intron_variant		1	NM_025130.4	ENSP00000346643	P1
	ENST00000450995.1	n.493+101C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33055 AN: 152004 Hom.: 4378 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.400 AC: 8 AN: 20 Hom.: 2 AF XY: 0.500 AC XY: 7 AN XY: 14

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.217 AC: 33048 AN: 152120 Hom.: 4379 Cov.: 32 AF XY: 0.215 AC XY: 15952 AN XY: 74356

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.219

Alfa AF: 0.274 Hom.: 1540

Bravo AF: 0.206

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.72

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: rs7089312; hg19: chr10-70982532;