rs4746822

Positions:

• chr10-69223185-C-T

Variant summary

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

The NM_025130.4(HKDC1):​c.63+2687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,022 control chromosomes in the GnomAD database, including 27,087 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 (27086 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: HKDC1 NM_025130.4 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=-0.87).
• 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	UniProt
HKDC1	NM_025130.4	c.63+2687C>T		intron_variant		ENST00000354624.6
LOC101928994	NR_120648.1	n.326G>A		non_coding_transcript_exon_variant	3/5
HKDC1	XM_011540195.3	c.63+2687C>T		intron_variant
HKDC1	XR_007061989.1	n.167+2687C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HKDC1	ENST00000354624.6	c.63+2687C>T		intron_variant		1	NM_025130.4	P1
	ENST00000450995.1	n.326G>A		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88934 AN: 151896 Hom.: 27052 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.551

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.586 AC: 89014 AN: 152014 Hom.: 27086 Cov.: 32 AF XY: 0.585 AC XY: 43492 AN XY: 74308

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.544

Alfa AF: 0.628 Hom.: 3960

Bravo AF: 0.561

Asia WGS AF: 0.407 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.56

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: rs4746822; hg19: chr10-70982941;