dbSNP rs749402818: PSTK:p.Ala4Gly (chr10-122980490-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001363531.2(PSTK):c.11C>G(p.Ala4Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PSTK
NM_001363531.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00200

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:

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ACMG classification

Classification made for transcript

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=0.07178569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSTK	NM_001363531.2 link	c.11C>G	p.Ala4Gly	missense_variant	Exon 1 of 6	ENST00000406217.8	NP_001350460.1
PSTK	NM_153336.3 link	c.11C>G	p.Ala4Gly	missense_variant	Exon 1 of 7		NP_699167.2	Q8IV42-1
PSTK	XM_017015641.3 link	c.11C>G	p.Ala4Gly	missense_variant	Exon 1 of 4		XP_016871130.1
PSTK	XR_001747018.2 link	n.90C>G		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSTK	ENST00000406217.8 link	c.11C>G	p.Ala4Gly	missense_variant	Exon 1 of 6	5	NM_001363531.2	ENSP00000384653.3		H7BYY4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000837

AC:

AN:

239022

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

131028

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1451244

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722064

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.5

DANN

Benign

0.92

DEOGEN2

Benign

0.015

T;.;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.46

.;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.56

N;.;N

REVEL

Benign

0.074

Sift

Benign

0.22

T;.;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0020

B;.;B

Vest4

0.031

MutPred

0.11

Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);

MVP

0.46

MPC

0.11

ClinPred

0.059

GERP RS

0.98

Varity_R

0.059

gMVP

0.53

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over