NM_002115.3:c.2349G>C

Variant names:

• chr5-176881736-C-G
• rs61755710
• NM_002115.3:c.2349G>C

Variant summary

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

The NM_002115.3(HK3):​c.2349G>C​(p.Gln783His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HK3 NM_002115.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 0 publications found

Genes affected

HK3 (HGNC:4925): (hexokinase 3) Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes hexokinase 3. Similar to hexokinases 1 and 2, this allosteric enzyme is inhibited by its product glucose-6-phosphate. [provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002115.3. 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
	HK3	NM_002115.3	MANE Select	c.2349G>C	p.Gln783His	missense	Exon 17 of 19	NP_002106.2	P52790

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK3	ENST00000292432.10	TSL:1 MANE Select	c.2349G>C	p.Gln783His	missense	Exon 17 of 19	ENSP00000292432.5	P52790
	HK3	ENST00000506834.5	TSL:1	n.1361G>C		non_coding_transcript_exon	Exon 8 of 10
	HK3	ENST00000874508.1		c.2349G>C	p.Gln783His	missense	Exon 17 of 19	ENSP00000544567.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Benign	0.87	L
PhyloP100		1.7
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.52
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.52
MutPred		0.47		Gain of MoRF binding (P = 0.1275)
MVP		0.94
MPC		0.44
ClinPred		0.90	D
GERP RS		3.7
Varity_R		0.23
gMVP		0.49
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61755710; hg19: chr5-176308737;