rs2611

Positions:

• chr10-69267475-G-C
• chr10-69267475-G-T

Variant summary

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

The NM_025130.4(HKDC1):​c.*718G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 454,846 control chromosomes in the GnomAD database, including 35,653 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 0.39 (11594 hom., cov: 32)
  • Exomes 𝑓: 0.39 (24059 hom.)
• Consequence: HKDC1 NM_025130.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HKDC1	NM_025130.4	c.*718G>C		3_prime_UTR_variant	18/18	ENST00000354624.6	NP_079406.4
HKDC1	XM_047425784.1	c.*718G>C		3_prime_UTR_variant	15/15		XP_047281740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6	c.*718G>C		3_prime_UTR_variant	18/18	1	NM_025130.4	ENSP00000346643	P1
	ENST00000413220.1	n.48+626C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58548 AN: 151914 Hom.: 11577 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.390

GnomAD3 exomes AF: 0.379 AC: 52529 AN: 138766 Hom.: 10488 AF XY: 0.392 AC XY: 29479 AN XY: 75176

Gnomad AFR exome AF: 0.451

Gnomad AMR exome AF: 0.274

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.371

Gnomad SAS exome AF: 0.516

Gnomad FIN exome AF: 0.316

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.389 AC: 117792 AN: 302814 Hom.: 24059 Cov.: 0 AF XY: 0.403 AC XY: 69517 AN XY: 172482

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.514

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.386 AC: 58611 AN: 152032 Hom.: 11594 Cov.: 32 AF XY: 0.384 AC XY: 28570 AN XY: 74334

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.393

Alfa AF: 0.388 Hom.: 2458

Bravo AF: 0.384

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.78

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: rs2611; hg19: chr10-71027231; COSMIC: COSV63577520; COSMIC: COSV63577520;