NM_033214.3:c.1496G>T

Variant names:

• chr4-79406705-C-A
• rs371254913
• NM_033214.3:c.1496G>T

Variant summary

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

The NM_033214.3(GK2):​c.1496G>T​(p.Arg499Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R499H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GK2 NM_033214.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

Genes affected

GK2 (HGNC:4291): (glycerol kinase 2) Predicted to enable glycerol kinase activity. Predicted to be involved in several processes, including glycerol metabolic process; glycerol-3-phosphate biosynthetic process; and triglyceride metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

GK2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

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_033214.3. 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
	GK2	NM_033214.3	MANE Select	c.1496G>T	p.Arg499Leu	missense	Exon 1 of 1	NP_149991.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GK2	ENST00000358842.5	TSL:6 MANE Select	c.1496G>T	p.Arg499Leu	missense	Exon 1 of 1	ENSP00000351706.3	Q14410

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.5
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.52
Sift	Benign	0.49	T
Sift4G	Benign	0.69	T
Polyphen		0.0070	B
Vest4		0.62
MutPred		0.57		Gain of glycosylation at T502 (P = 0.0088)
MVP		0.84
MPC		0.10
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.45
gMVP		0.87
Mutation Taster		=56/44	polymorphism

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: rs371254913; hg19: chr4-80327859;