3-52290514-G-C

Position:

• chr3-52290514-G-C

Variant summary

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

The NM_145262.4(GLYCTK):​c.172G>C​(p.Ala58Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLYCTK NM_145262.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

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.172G>C	p.Ala58Pro	missense_variant	2/5	ENST00000436784.7	NP_660305.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYCTK	ENST00000436784.7	c.172G>C	p.Ala58Pro	missense_variant	2/5	1	NM_145262.4	ENSP00000389175	P1
GLYCTK-AS1	ENST00000493616.1	n.304-1790C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.172G>C (p.A58P) alteration is located in exon 2 (coding exon 1) of the GLYCTK gene. This alteration results from a G to C substitution at nucleotide position 172, causing the alanine (A) at amino acid position 58 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;.;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T;T;.
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.60	D;D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	3.3	M;M;M;M
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.065	T;T;D;D
Sift4G	Uncertain	0.056	T;T;T;T
Polyphen		0.98	D;.;P;D
Vest4		0.57
MutPred		0.48		Gain of disorder (P = 0.0249);Gain of disorder (P = 0.0249);Gain of disorder (P = 0.0249);Gain of disorder (P = 0.0249);
MVP		0.58
MPC		0.44
ClinPred		0.67	D
GERP RS		0.55
Varity_R		0.87
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-52324530;