chrX-30668064-G-C

Variant names:

• chrX-30668064-G-C
• NM_001205019.2:c.205G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001205019.2(GK):​c.205G>C​(p.Glu69Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: GK NM_001205019.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40755394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2	c.205G>C	p.Glu69Gln	missense_variant	Exon 3 of 21	ENST00000427190.6	NP_001191948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GK	ENST00000427190.6	c.205G>C	p.Glu69Gln	missense_variant	Exon 3 of 21	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.205G>C (p.E69Q) alteration is located in exon 3 (coding exon 3) of the GK gene. This alteration results from a G to C substitution at nucleotide position 205, causing the glutamic acid (E) at amino acid position 69 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;.;T;.;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.41	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;L;L;L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.4	N;N;.;N;N
REVEL	Benign	0.18
Sift	Benign	0.23	T;T;.;T;T
Sift4G	Benign	0.41	T;T;T;T;T
Polyphen		0.70	.;P;.;P;.
Vest4		0.50
MutPred		0.52		Loss of ubiquitination at K74 (P = 0.1016);Loss of ubiquitination at K74 (P = 0.1016);Loss of ubiquitination at K74 (P = 0.1016);Loss of ubiquitination at K74 (P = 0.1016);Loss of ubiquitination at K74 (P = 0.1016);
MVP		0.62
MPC		1.6
ClinPred		0.88	D
GERP RS		5.6
Varity_R		0.58
gMVP		0.67

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-30686181;