10-122980618-G-T

Position:

• chr10-122980618-G-T

Variant summary

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

The NM_001363531.2(PSTK):​c.139G>T​(p.Gly47Cys) 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 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: 2.69

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, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSTK	NM_001363531.2	c.139G>T	p.Gly47Cys	missense_variant	1/6	ENST00000406217.8	NP_001350460.1
PSTK	NM_153336.3	c.139G>T	p.Gly47Cys	missense_variant	1/7		NP_699167.2
PSTK	XM_017015641.3	c.139G>T	p.Gly47Cys	missense_variant	1/4		XP_016871130.1
PSTK	XR_001747018.2	n.218G>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSTK	ENST00000406217.8	c.139G>T	p.Gly47Cys	missense_variant	1/6	5	NM_001363531.2	ENSP00000384653.3

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

Aug 04, 2024

The c.139G>T (p.G47C) alteration is located in exon 1 (coding exon 1) of the PSTK gene. This alteration results from a G to T substitution at nucleotide position 139, causing the glycine (G) at amino acid position 47 to be replaced by a cysteine (C). 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	0.20
BayesDel_addAF	Benign	-0.0042	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.044
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.73	.;T;T
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Pathogenic	3.3	M;.;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.8	D;.;D
REVEL	Benign	0.28
Sift	Benign	0.087	T;.;T
Sift4G	Benign	0.093	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.32
MutPred		0.80		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.86
MPC		0.53
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.41
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1210702279; hg19: chr10-124740134;