3-52291039-C-G

Variant names:

• chr3-52291039-C-G
• rs199906865
• NM_145262.4:c.457C>G

Variant summary

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

The NM_145262.4(GLYCTK):​c.457C>G​(p.Arg153Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R153W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLYCTK NM_145262.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 4 publications found

Genes affected

GLYCTK (HGNC:24247): (glycerate kinase) This locus encodes a member of the glycerate kinase type-2 family. The encoded enzyme catalyzes the phosphorylation of (R)-glycerate and may be involved in serine degradation and fructose metabolism. Decreased activity of the encoded enzyme may be associated with the disease D-glyceric aciduria. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2009]

GLYCTK-AS1 (HGNC:41043): (GLYCTK antisense RNA 1)

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_145262.4. 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
	GLYCTK	NM_145262.4	MANE Select	c.457C>G	p.Arg153Gly	missense	Exon 3 of 5	NP_660305.2
	GLYCTK	NM_001437621.1		c.457C>G	p.Arg153Gly	missense	Exon 2 of 4	NP_001424550.1
	GLYCTK	NM_001144951.2		c.457C>G	p.Arg153Gly	missense	Exon 3 of 4	NP_001138423.1	Q8IVS8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLYCTK	ENST00000436784.7	TSL:1 MANE Select	c.457C>G	p.Arg153Gly	missense	Exon 3 of 5	ENSP00000389175.2	Q8IVS8-1
	GLYCTK	ENST00000477382.2	TSL:1	c.457C>G	p.Arg153Gly	missense	Exon 3 of 4	ENSP00000419008.1
	GLYCTK	ENST00000473032.5	TSL:1	c.457C>G	p.Arg153Gly	missense	Exon 3 of 5	ENSP00000418951.1	Q8IVS8-7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.1
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.27
Sift	Benign	0.073	T
Sift4G	Benign	0.29	T
Varity_R		0.24
gMVP		0.51
Mutation Taster		=90/10	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs199906865; hg19: chr3-52325055;