rs202105296

chr10-69243340-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025130.4(HKDC1):c.850G>A(p.Gly284Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000881 in 1,599,932 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (1 hom.)
• Consequence: HKDC1 NM_025130.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.90

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04363337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HKDC1	NM_025130.4	c.850G>A	p.Gly284Ser	missense_variant	7/18	ENST00000354624.6
HKDC1	XM_011540195.3	c.850G>A	p.Gly284Ser	missense_variant	7/16
HKDC1	XM_047425784.1	c.274G>A	p.Gly92Ser	missense_variant	4/15
HKDC1	XR_007061989.1	n.954G>A		non_coding_transcript_exon_variant	7/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HKDC1	ENST00000354624.6	c.850G>A	p.Gly284Ser	missense_variant	7/18	1	NM_025130.4	P1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000847 AC: 20 AN: 236222 Hom.: 0 AF XY: 0.0000943 AC XY: 12 AN XY: 127244

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000364

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000188

Gnomad OTH exome AF: 0.000349

GnomAD4 exome AF: 0.0000746 AC: 108 AN: 1447658 Hom.: 1 Cov.: 31 AF XY: 0.0000640 AC XY: 46 AN XY: 719118

Gnomad4 AFR exome AF: 0.000151

Gnomad4 AMR exome AF: 0.000992

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000244

Gnomad4 OTH exome AF: 0.000452

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74446

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000227 Hom.: 1

Bravo AF: 0.000366

ExAC AF: 0.0000577 AC: 7

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Keratoconus 1 Uncertain:1

Uncertain significance, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Apr 21, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Uncertain	0.010
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.044	T
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.51
Sift	Benign	0.35	T
Sift4G	Benign	0.18	T
Polyphen		0.12	B
Vest4		0.57
MVP		0.91
MPC		0.29
ClinPred		0.042	T
GERP RS		5.2
Varity_R		0.29
gMVP		0.67

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: rs202105296; hg19: chr10-71003096;