5-176881735-T-C

Position:

• chr5-176881735-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002115.3(HK3):​c.2350A>G​(p.Thr784Ala) 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HK3 NM_002115.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

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]

HK3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4157293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HK3	NM_002115.3	c.2350A>G	p.Thr784Ala	missense_variant	17/19	ENST00000292432.10	NP_002106.2
HK3	XM_047417134.1	c.2253A>G	p.Arg751Arg	synonymous_variant	17/18		XP_047273090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HK3	ENST00000292432.10	c.2350A>G	p.Thr784Ala	missense_variant	17/19	1	NM_002115.3	ENSP00000292432.5
HK3	ENST00000506834.5	n.1362A>G		non_coding_transcript_exon_variant	8/10	1
HK3	ENST00000514666.1	n.138A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.2350A>G (p.T784A) alteration is located in exon 17 (coding exon 16) of the HK3 gene. This alteration results from a A to G substitution at nucleotide position 2350, causing the threonine (T) at amino acid position 784 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.025
Eigen_PC	Benign	0.00049
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.42	T
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.48
Sift	Benign	0.044	D
Sift4G	Uncertain	0.048	D
Polyphen		0.0060	B
Vest4		0.36
MutPred		0.55		Loss of phosphorylation at T784 (P = 0.0579);
MVP		0.95
MPC		0.11
ClinPred		0.80	D
GERP RS		2.0
Varity_R		0.28
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-176308736;