10-122980525-C-T

Variant names:

• chr10-122980525-C-T
• rs1456567659
• NM_001363531.2:c.46C>T

Variant summary

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

The NM_001363531.2(PSTK):​c.46C>T​(p.Arg16Trp) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSTK NM_001363531.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0170

Genes affected

PSTK (HGNC:28578): (phosphoseryl-tRNA kinase) Predicted to enable kinase activity and tRNA binding activity. Predicted to be involved in phosphorylation; selenocysteinyl-tRNA(Sec) biosynthetic process; and translation. Predicted to act upstream of or within selenocysteine incorporation. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18685293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSTK	NM_001363531.2	c.46C>T	p.Arg16Trp	missense_variant	Exon 1 of 6	ENST00000406217.8	NP_001350460.1
PSTK	NM_153336.3	c.46C>T	p.Arg16Trp	missense_variant	Exon 1 of 7		NP_699167.2
PSTK	XM_017015641.3	c.46C>T	p.Arg16Trp	missense_variant	Exon 1 of 4		XP_016871130.1
PSTK	XR_001747018.2	n.125C>T		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSTK	ENST00000406217.8	c.46C>T	p.Arg16Trp	missense_variant	Exon 1 of 6	5	NM_001363531.2	ENSP00000384653.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.46C>T (p.R16W) alteration is located in exon 1 (coding exon 1) of the PSTK gene. This alteration results from a C to T substitution at nucleotide position 46, causing the arginine (R) at amino acid position 16 to be replaced by a tryptophan (W). 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	Benign	0.10
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.78	.;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.0	M;.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.3	N;.;N
REVEL	Benign	0.094
Sift	Uncertain	0.0060	D;.;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.18
MutPred		0.41		Loss of disorder (P = 8e-04);Loss of disorder (P = 8e-04);Loss of disorder (P = 8e-04);
MVP		0.53
MPC		0.39
ClinPred		0.81	D
GERP RS		0.13
Varity_R		0.089
gMVP		0.62

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: rs1456567659; hg19: chr10-124740041;