chrX-30653592-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001205019.2(GK):​c.55G>C​(p.Gly19Arg) variant causes a missense change. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

GK
NM_001205019.2 missense

Scores

14
2
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06
Variant links:
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.987

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GKNM_001205019.2 linkc.55G>C p.Gly19Arg missense_variant Exon 1 of 21 ENST00000427190.6 NP_001191948.1 P32189-3B4DH54

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GKENST00000427190.6 linkc.55G>C p.Gly19Arg missense_variant Exon 1 of 21 5 NM_001205019.2 ENSP00000401720.2 P32189-3

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

See cases Uncertain:1
Apr 13, 2023
Institute of Human Genetics, University Hospital Muenster
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ACMG categories: PM1,PM2,PP3 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.59
D
BayesDel_noAF
Pathogenic
0.60
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.45
.;.;T;.;.
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D
M_CAP
Pathogenic
0.98
D
MetaRNN
Pathogenic
0.99
D;D;D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
5.1
H;H;H;H;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-6.9
D;D;N;D;D
REVEL
Pathogenic
0.89
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
1.0
.;D;.;D;.
Vest4
0.82
MutPred
0.93
Gain of MoRF binding (P = 0.0615);Gain of MoRF binding (P = 0.0615);Gain of MoRF binding (P = 0.0615);Gain of MoRF binding (P = 0.0615);Gain of MoRF binding (P = 0.0615);
MVP
0.99
MPC
2.4
ClinPred
1.0
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.98
gMVP
0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-30671709; API