rs199906865

Positions:

• chr3-52291039-C-G
• chr3-52291039-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYCTK	NM_145262.4	c.457C>G	p.Arg153Gly	missense_variant	3/5	ENST00000436784.7	NP_660305.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYCTK	ENST00000436784.7	c.457C>G	p.Arg153Gly	missense_variant	3/5	1	NM_145262.4	ENSP00000389175	P1
GLYCTK-AS1	ENST00000493616.1	n.303+1988G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D;D;D;.
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.67	D;D;D;D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.4	.;M;M;.;M;M
MutationTaster	Benign	0.56	D;D;D;D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	D;N;N;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.073	T;T;T;T;T;D
Sift4G	Benign	0.29	T;T;T;T;T;T
Polyphen		0.98, 0.64	.;D;.;.;P;D
Vest4		0.58
MutPred		0.49		.;Gain of catalytic residue at A154 (P = 0.0435);Gain of catalytic residue at A154 (P = 0.0435);.;Gain of catalytic residue at A154 (P = 0.0435);Gain of catalytic residue at A154 (P = 0.0435);
MVP		0.67
MPC		0.33
ClinPred		0.84	D
GERP RS		3.2
Varity_R		0.24
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs199906865; hg19: chr3-52325055;