NM_001205019.2:c.106C>T

Variant names:

• chrX-30665538-C-T
• rs1933013956
• NM_001205019.2:c.106C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001205019.2(GK):​c.106C>T​(p.Leu36Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: GK NM_001205019.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.74
• Publications: 0 publications found

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]

GK Gene-Disease associations (from GenCC):

• inborn glycerol kinase deficiency

  Inheritance: XL, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205019.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GK	NM_001205019.2	MANE Select	c.106C>T	p.Leu36Phe	missense	Exon 2 of 21	NP_001191948.1	P32189-3
	GK	NM_001437590.1		c.106C>T	p.Leu36Phe	missense	Exon 2 of 21	NP_001424519.1	A0A8I5KXY7
	GK	NM_001128127.3		c.106C>T	p.Leu36Phe	missense	Exon 2 of 20	NP_001121599.1	P32189-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GK	ENST00000427190.6	TSL:5 MANE Select	c.106C>T	p.Leu36Phe	missense	Exon 2 of 21	ENSP00000401720.2	P32189-3
	GK	ENST00000378943.7	TSL:1	c.106C>T	p.Leu36Phe	missense	Exon 2 of 20	ENSP00000368226.3	P32189-2
	GK	ENST00000378946.7	TSL:1	c.106C>T	p.Leu36Phe	missense	Exon 2 of 20	ENSP00000368229.3	P32189-4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn glycerol kinase deficiency (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.033	D
Polyphen		0.92	P
Vest4		0.65
MutPred		0.56		Gain of catalytic residue at L36 (P = 0.0362)
MVP		0.69
MPC		2.1
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.77
gMVP		0.79
Mutation Taster		=21/79	disease causing

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

Other links and lift over

dbSNP: rs1933013956; hg19: chrX-30683655;