rs540302092

Variant names:

• chr5-176881530-C-A
• NM_002115.3:c.2399G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-176881530-C-A
• chr5-176881530-C-T

Variant summary

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

The NM_002115.3(HK3):​c.2399G>T​(p.Ser800Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,449,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S800N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HK3 NM_002115.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86

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

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=0.3848534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HK3	NM_002115.3	c.2399G>T	p.Ser800Ile	missense_variant	Exon 18 of 19	ENST00000292432.10	NP_002106.2
HK3	XM_047417134.1	c.2302G>T	p.Ala768Ser	missense_variant	Exon 18 of 18		XP_047273090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HK3	ENST00000292432.10	c.2399G>T	p.Ser800Ile	missense_variant	Exon 18 of 19	1	NM_002115.3	ENSP00000292432.5
HK3	ENST00000506834.5	n.1411G>T		non_coding_transcript_exon_variant	Exon 9 of 10	1
HK3	ENST00000514666.1	n.187G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449764 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 720732

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.033
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	0.75	D
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.42
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		0.17	B
Vest4		0.49
MutPred		0.59		Loss of disorder (P = 0.0073);
MVP		0.97
MPC		0.54
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.37
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr5-176308531;