chr4-79406705-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_033214.3(GK2):​c.1496G>A​(p.Arg499His) variant causes a missense change. The variant allele was found at a frequency of 0.000198 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: GK2 NM_033214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.54
• Publications: 2 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27738953).

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>A	p.Arg499His	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>A	p.Arg499His	missense	Exon 1 of 1	ENSP00000351706.3	Q14410

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000115 AC: 29 AN: 251486 AF XY: 0.000103

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000207 AC: 303 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 146 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 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: 0.000258 AC: 287 AN: 1112006

Other (OTH) AF: 0.000182 AC: 11 AN: 60396

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74334

African (AFR) AF: 0.0000965 AC: 4 AN: 41460

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000965 Hom.: 0

Bravo AF: 0.0000907

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.5
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.39
Sift	Benign	0.11	T
Sift4G	Benign	0.25	T
Polyphen		0.016	B
Vest4		0.32
MVP		0.87
MPC		0.10
ClinPred		0.21	T
GERP RS		3.9
Varity_R		0.23
gMVP		0.81
Mutation Taster		=66/34	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; COSMIC: COSV62626515;