10-122986901-T-G

Position:

• chr10-122986901-T-G

Variant summary

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

The NM_001363531.2(PSTK):​c.816T>G​(p.Ile272Met) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PSTK NM_001363531.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.112

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=0.13065195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSTK	NM_001363531.2	c.816T>G	p.Ile272Met	missense_variant	5/6	ENST00000406217.8	NP_001350460.1
PSTK	NM_153336.3	c.816T>G	p.Ile272Met	missense_variant	5/7		NP_699167.2
PSTK	XM_017015641.3	c.708-3273T>G		intron_variant			XP_016871130.1
PSTK	XR_001747018.2	n.895T>G		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSTK	ENST00000406217.8	c.816T>G	p.Ile272Met	missense_variant	5/6	5	NM_001363531.2	ENSP00000384653	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Dec 18, 2023

The c.816T>G (p.I272M) alteration is located in exon 5 (coding exon 5) of the PSTK gene. This alteration results from a T to G substitution at nucleotide position 816, causing the isoleucine (I) at amino acid position 272 to be replaced by a methionine (M). 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	0.089
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.7
DANN	Benign	0.82
DEOGEN2	Benign	0.017	T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.48	.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L;.;L
MutationTaster	Benign	0.57	D;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.97	N;.;.
REVEL	Benign	0.13
Sift	Uncertain	0.024	D;.;.
Sift4G	Benign	0.093	T;T;T
Polyphen		0.25	B;.;B
Vest4		0.27
MutPred		0.65		Gain of disorder (P = 0.0337);Gain of disorder (P = 0.0337);Gain of disorder (P = 0.0337);
MVP		0.23
MPC		0.20
ClinPred		0.11	T
GERP RS		-2.5
Varity_R		0.11
gMVP		0.27

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: chr10-124746417;