10-122980525-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0170
Variant links:
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]

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ACMG classification

Classification made for transcript

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
PSTKNM_001363531.2 linkc.46C>T p.Arg16Trp missense_variant Exon 1 of 6 ENST00000406217.8 NP_001350460.1
PSTKNM_153336.3 linkc.46C>T p.Arg16Trp missense_variant Exon 1 of 7 NP_699167.2 Q8IV42-1
PSTKXM_017015641.3 linkc.46C>T p.Arg16Trp missense_variant Exon 1 of 4 XP_016871130.1
PSTKXR_001747018.2 linkn.125C>T non_coding_transcript_exon_variant Exon 1 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PSTKENST00000406217.8 linkc.46C>T p.Arg16Trp missense_variant Exon 1 of 6 5 NM_001363531.2 ENSP00000384653.3 H7BYY4

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
LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1456567659; hg19: chr10-124740041; API