10-122982733-C-T

Position:

• chr10-122982733-C-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.217C>T​(p.Pro73Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PSTK NM_001363531.2 missense, splice_region
• Scores: Splicing: ADA: 0.001961
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.363

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=0.16149849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSTK	NM_001363531.2	c.217C>T	p.Pro73Ser	missense_variant, splice_region_variant	2/6	ENST00000406217.8	NP_001350460.1
PSTK	NM_153336.3	c.217C>T	p.Pro73Ser	missense_variant, splice_region_variant	2/7		NP_699167.2
PSTK	XM_017015641.3	c.217C>T	p.Pro73Ser	missense_variant, splice_region_variant	2/4		XP_016871130.1
PSTK	XR_001747018.2	n.296C>T		splice_region_variant, non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSTK	ENST00000406217.8	c.217C>T	p.Pro73Ser	missense_variant, splice_region_variant	2/6	5	NM_001363531.2	ENSP00000384653	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461462 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

May 18, 2023

The c.217C>T (p.P73S) alteration is located in exon 2 (coding exon 2) of the PSTK gene. This alteration results from a C to T substitution at nucleotide position 217, causing the proline (P) at amino acid position 73 to be replaced by a serine (S). 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	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.010	T;.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.64	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L;.;L
MutationTaster	Benign	0.53	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.69	N;.;N
REVEL	Benign	0.084
Sift	Benign	0.42	T;.;T
Sift4G	Benign	0.82	T;T;T
Polyphen		0.029	B;.;B
Vest4		0.098
MutPred		0.62		Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);
MVP		0.53
MPC		0.13
ClinPred		0.091	T
GERP RS		3.7
Varity_R		0.034
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0020
dbscSNV1_RF	Benign	0.17
SpliceAI score (max)		0.070		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: rs1848979126; hg19: chr10-124742249;