10-69266754-C-G

Variant names:

• chr10-69266754-C-G
• rs906219
• NM_025130.4:c.2751C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000354624.6(HKDC1):​c.2751C>G​(p.Asn917Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HKDC1 ENST00000354624.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 35 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000231748 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083082855).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354624.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HKDC1	NM_025130.4	MANE Select	c.2751C>G	p.Asn917Lys	missense	Exon 18 of 18	NP_079406.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HKDC1	ENST00000354624.6	TSL:1 MANE Select	c.2751C>G	p.Asn917Lys	missense	Exon 18 of 18	ENSP00000346643.5
	ENSG00000231748	ENST00000413220.1	TSL:3	n.49-1027G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.083	T
MetaSVM	Uncertain	0.043	D
MutationAssessor	Benign	-0.20	N
PhyloP100		1.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.24
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.041	D
Polyphen		0.0	B
Vest4		0.059
MutPred		0.14		Gain of MoRF binding (P = 0.0366)
MVP		0.56
MPC		0.16
ClinPred		0.12	T
GERP RS		0.70
Varity_R		0.11
gMVP		0.43
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs906219; hg19: chr10-71026510;