10-69222776-G-C

Variant names:

• chr10-69222776-G-C
• rs7089312
• NM_025130.4:c.63+2278G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025130.4(HKDC1):​c.63+2278G>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HKDC1 NM_025130.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 3 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

ENSG00000229261 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HKDC1	NM_025130.4	c.63+2278G>C		intron_variant	Intron 1 of 17	ENST00000354624.6	NP_079406.4
LOC101928994	NR_120648.1	n.493+101C>G		intron_variant	Intron 4 of 4
HKDC1	XM_011540195.3	c.63+2278G>C		intron_variant	Intron 1 of 15		XP_011538497.1
HKDC1	XR_007061989.1	n.167+2278G>C		intron_variant	Intron 1 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6	c.63+2278G>C		intron_variant	Intron 1 of 17	1	NM_025130.4	ENSP00000346643.5
ENSG00000229261	ENST00000450995.1	n.493+101C>G		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2888

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.63
PhyloP100		0.42

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: rs7089312; hg19: chr10-70982532;