10-69288744-A-G
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_001358263.1(HK1):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
HK1
NM_001358263.1 start_lost
NM_001358263.1 start_lost
Scores
5
3
4
Clinical Significance
Conservation
PhyloP100: 3.39
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 Pathogenic. Variant got 14 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_001358263.1 (HK1) was described as [Likely_pathogenic] in ClinVar as 1685345
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 10-69288744-A-G is Pathogenic according to our data. Variant chr10-69288744-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 802580.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HK1 | NM_001358263.1 | c.1A>G | p.Met1? | start_lost | 3/21 | ENST00000643399.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HK1 | ENST00000643399.2 | c.1A>G | p.Met1? | start_lost | 3/21 | NM_001358263.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 4G Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D
PROVEAN
Benign
N;N;N;.;.;.
Sift
Pathogenic
D;D;D;.;.;.
Polyphen
B;.;B;.;.;B
Vest4
0.86
MutPred
Loss of catalytic residue at M1 (P = 0.0295);Loss of catalytic residue at M1 (P = 0.0295);Loss of catalytic residue at M1 (P = 0.0295);Loss of catalytic residue at M1 (P = 0.0295);Loss of catalytic residue at M1 (P = 0.0295);Loss of catalytic residue at M1 (P = 0.0295);
MVP
0.81
ClinPred
D
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at