10-122980550-G-A

Position:

• chr10-122980550-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001363531.2(PSTK):​c.71G>A​(p.Cys24Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 5.58

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSTK	NM_001363531.2	c.71G>A	p.Cys24Tyr	missense_variant	1/6	ENST00000406217.8	NP_001350460.1
PSTK	NM_153336.3	c.71G>A	p.Cys24Tyr	missense_variant	1/7		NP_699167.2
PSTK	XM_017015641.3	c.71G>A	p.Cys24Tyr	missense_variant	1/4		XP_016871130.1
PSTK	XR_001747018.2	n.150G>A		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSTK	ENST00000406217.8	c.71G>A	p.Cys24Tyr	missense_variant	1/6	5	NM_001363531.2	ENSP00000384653	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Mar 13, 2023

The c.71G>A (p.C24Y) alteration is located in exon 1 (coding exon 1) of the PSTK gene. This alteration results from a G to A substitution at nucleotide position 71, causing the cysteine (C) at amino acid position 24 to be replaced by a tyrosine (Y). 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	0.81
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	2.9	M;.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.1	D;.;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.025	D;.;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.97	D;.;D
Vest4		0.79
MutPred		0.71		Gain of phosphorylation at C24 (P = 0.0505);Gain of phosphorylation at C24 (P = 0.0505);Gain of phosphorylation at C24 (P = 0.0505);
MVP		0.48
MPC		0.69
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.71
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-124740066;