chrX-30668107-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001205019.2(GK):c.248C>T(p.Ser83Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000114 in 873,641 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000011 ( 0 hom. 1 hem. )
Consequence
GK
NM_001205019.2 missense
NM_001205019.2 missense
Scores
2
7
7
Clinical Significance
Conservation
PhyloP100: 7.51
Genes affected
GK (HGNC:4289): (glycerol kinase) The protein encoded by this gene belongs to the FGGY kinase family. This protein is a key enzyme in the regulation of glycerol uptake and metabolism. It catalyzes the phosphorylation of glycerol by ATP, yielding ADP and glycerol-3-phosphate. Mutations in this gene are associated with glycerol kinase deficiency (GKD). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
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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 gene, where missense usually causes diseases (based on misZ statistic), GK. . Gene score misZ 3.1858 (greater than the threshold 3.09). GenCC has associacion of gene with inborn glycerol kinase deficiency.
BP4
Computational evidence support a benign effect (MetaRNN=0.41140664).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GK | NM_001205019.2 | c.248C>T | p.Ser83Phe | missense_variant | 3/21 | ENST00000427190.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GK | ENST00000427190.6 | c.248C>T | p.Ser83Phe | missense_variant | 3/21 | 5 | NM_001205019.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
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23
GnomAD3 exomes AF: 0.00000548 AC: 1AN: 182494Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67226
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GnomAD4 exome AF: 0.00000114 AC: 1AN: 873641Hom.: 0 Cov.: 17 AF XY: 0.00000408 AC XY: 1AN XY: 244923
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GnomAD4 genome Cov.: 23
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23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 17, 2019 | Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;D;D
REVEL
Benign
Sift
Uncertain
D;D;.;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
0.53
.;P;.;P;.
Vest4
MutPred
Loss of catalytic residue at S83 (P = 0.0519);Loss of catalytic residue at S83 (P = 0.0519);Loss of catalytic residue at S83 (P = 0.0519);Loss of catalytic residue at S83 (P = 0.0519);Loss of catalytic residue at S83 (P = 0.0519);
MVP
MPC
1.8
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at