NM_001358263.1:c.1455G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_001358263.1(HK1):​c.1455G>C​(p.Lys485Asn) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K485K) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

HK1
NM_001358263.1 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.894
Variant links:
Genes affected
HK1 (HGNC:4922): (hexokinase 1) Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in several transcript variants which encode different isoforms, some of which are tissue-specific. [provided by RefSeq, Apr 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the HK1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 13 curated pathogenic missense variants (we use a threshold of 10). The gene has 22 curated benign missense variants. Trascript score misZ: 5.1108 (above the threshold of 3.09). GenCC associations: The gene is linked to retinitis pigmentosa 79, non-spherocytic hemolytic anemia due to hexokinase deficiency, neurodevelopmental disorder with visual defects and brain anomalies, Charcot-Marie-Tooth disease type 4G.
BP4
Computational evidence support a benign effect (MetaRNN=0.37756994).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HK1NM_001358263.1 linkc.1455G>C p.Lys485Asn missense_variant Exon 13 of 21 ENST00000643399.2 NP_001345192.1
HK1NM_000188.3 linkc.1443G>C p.Lys481Asn missense_variant Exon 10 of 18 ENST00000359426.7 NP_000179.2 P19367-1B3KXY9A8K7J7Q59FD4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HK1ENST00000643399.2 linkc.1455G>C p.Lys485Asn missense_variant Exon 13 of 21 NM_001358263.1 ENSP00000494664.1 P19367-3
HK1ENST00000359426.7 linkc.1443G>C p.Lys481Asn missense_variant Exon 10 of 18 1 NM_000188.3 ENSP00000352398.6 P19367-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
67
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Uncertain
0.034
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.42
.;.;.;.;.;T
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.68
.;T;T;.;T;T
M_CAP
Uncertain
0.094
D
MetaRNN
Benign
0.38
T;T;T;T;T;T
MetaSVM
Uncertain
0.29
D
MutationAssessor
Benign
0.47
.;.;.;.;.;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.98
.;.;N;.;N;N
REVEL
Uncertain
0.36
Sift
Benign
0.55
.;.;T;.;T;T
Sift4G
Benign
0.52
.;T;T;.;T;T
Polyphen
0.0
B;B;B;B;B;B
Vest4
0.21, 0.21, 0.23, 0.23
MVP
0.72
ClinPred
0.10
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.78

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748235; hg19: chr10-71142420; API