chrX-30668056-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001205019.2(GK):ā€‹c.197A>Cā€‹(p.Glu66Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000976 in 1,024,505 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 24)
Exomes š‘“: 9.8e-7 ( 0 hom. 0 hem. )

Consequence

GK
NM_001205019.2 missense

Scores

1
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.87
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GKNM_001205019.2 linkc.197A>C p.Glu66Ala missense_variant Exon 3 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.197A>C p.Glu66Ala missense_variant Exon 3 of 21 5 NM_001205019.2 ENSP00000401720.2 P32189-3

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
9.76e-7
AC:
1
AN:
1024505
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
311063
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000129
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24

ClinVar

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

Submissions by phenotype

Inborn glycerol kinase deficiency Uncertain:1
Aug 06, 2021
New York Genome Center
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
.;.;T;.;.
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.97
D;D;D;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.55
D;D;D;D;D
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.5
L;L;L;L;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-2.6
D;D;.;D;D
REVEL
Uncertain
0.36
Sift
Benign
0.14
T;T;.;T;T
Sift4G
Benign
0.38
T;T;T;T;T
Polyphen
0.28, 0.17
.;B;.;B;.
Vest4
0.55
MutPred
0.49
Loss of ubiquitination at K70 (P = 0.198);Loss of ubiquitination at K70 (P = 0.198);Loss of ubiquitination at K70 (P = 0.198);Loss of ubiquitination at K70 (P = 0.198);Loss of ubiquitination at K70 (P = 0.198);
MVP
0.58
MPC
1.2
ClinPred
0.90
D
GERP RS
5.6
Varity_R
0.73
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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-30686173; API