Variant 10-122980519-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001363531.2(PSTK):c.40G>A(p.Gly14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,456,336 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 32)

Exomes 𝑓: 0.000019 ( 1 hom. )

Consequence

PSTK
NM_001363531.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.136

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]

PSTK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045419008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PSTK	NM_001363531.2 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	1/6	ENST00000406217.8	NP_001350460.1
PSTK	NM_153336.3 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	1/7		NP_699167.2
PSTK	XM_017015641.3 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	1/4		XP_016871130.1
PSTK	XR_001747018.2 linkuse as main transcript	n.119G>A		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSTK	ENST00000406217.8 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	1/6	5	NM_001363531.2	ENSP00000384653	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000293

AC:

AN:

239216

Hom.:

AF XY:

0.0000380

AC XY:

AN XY:

131466

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1456336

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

724544

show subpopulations

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:

0.000314

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2023

The c.40G>A (p.G14R) 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 40, causing the glycine (G) at amino acid position 14 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.6

DANN

Benign

0.88

DEOGEN2

Benign

0.0071

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.55

.;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.17

N;.;N

REVEL

Benign

0.027

Sift

Benign

0.21

T;.;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.027

B;.;B

Vest4

0.12

MutPred

0.17

Gain of MoRF binding (P = 0.0103);Gain of MoRF binding (P = 0.0103);Gain of MoRF binding (P = 0.0103);

MVP

0.52

MPC

0.14

ClinPred

0.070

GERP RS

1.4

Varity_R

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over