rs1564726619

Variant names:

• chr10-69232838-G-C
• rs1564726619
• NM_025130.4:c.301G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-69232838-G-C
• chr10-69232838-G-T
• chr10-69232838-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PM5 BP4

The NM_025130.4(HKDC1):​c.301G>C​(p.Gly101Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G101W) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HKDC1 NM_025130.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.54
• Publications: 0 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr10-69232838-G-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 599515.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.27732626).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025130.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HKDC1	NM_025130.4	MANE Select	c.301G>C	p.Gly101Arg	missense	Exon 3 of 18	NP_079406.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HKDC1	ENST00000354624.6	TSL:1 MANE Select	c.301G>C	p.Gly101Arg	missense	Exon 3 of 18	ENSP00000346643.5	Q2TB90-1
	HKDC1	ENST00000953956.1		c.301G>C	p.Gly101Arg	missense	Exon 3 of 17	ENSP00000624015.1
	HKDC1	ENST00000953957.1		c.301G>C	p.Gly101Arg	missense	Exon 3 of 10	ENSP00000624016.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.039
Eigen_PC	Benign	0.085
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.28	T
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Benign	0.79	N
PhyloP100		6.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.52
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.012	D
Polyphen		0.027	B
Vest4		0.32
MutPred		0.47		Gain of solvent accessibility (P = 0.0097)
MVP		0.88
MPC		0.19
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.56
gMVP		0.64
Mutation Taster		=47/53	disease causing

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: rs1564726619; hg19: chr10-70992594;