3-52290385-C-T

Position:

• chr3-52290385-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145262.4(GLYCTK):​c.43C>T​(p.Pro15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLYCTK NM_145262.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11783332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLYCTK	NM_145262.4	c.43C>T	p.Pro15Ser	missense_variant	2/5	ENST00000436784.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLYCTK	ENST00000436784.7	c.43C>T	p.Pro15Ser	missense_variant	2/5	1	NM_145262.4	P1
GLYCTK-AS1	ENST00000493616.1	n.304-1661G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.81	T;T;T;.
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;M;M
MutationTaster	Benign	1.0	D;D;N;N;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.24	N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.15	T;D;T;D
Sift4G	Uncertain	0.058	T;T;T;T
Polyphen		0.029	B;.;B;B
Vest4		0.28
MutPred		0.34		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.46
MPC		0.16
ClinPred		0.16	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
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: rs1041353712; hg19: chr3-52324401;