10-122980523-C-A

Variant names:

• chr10-122980523-C-A
• rs983685436
• NM_001363531.2:c.44C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363531.2(PSTK):​c.44C>A​(p.Pro15Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P15T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PSTK NM_001363531.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088288754).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363531.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSTK	NM_001363531.2	MANE Select	c.44C>A	p.Pro15Gln	missense	Exon 1 of 6	NP_001350460.1	H7BYY4
	PSTK	NM_153336.3		c.44C>A	p.Pro15Gln	missense	Exon 1 of 7	NP_699167.2	Q8IV42-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSTK	ENST00000406217.8	TSL:5 MANE Select	c.44C>A	p.Pro15Gln	missense	Exon 1 of 6	ENSP00000384653.3	H7BYY4
	PSTK	ENST00000368887.7	TSL:1	c.44C>A	p.Pro15Gln	missense	Exon 1 of 7	ENSP00000357882.3	Q8IV42-1
	PSTK	ENST00000405485.2	TSL:2	c.44C>A	p.Pro15Gln	missense	Exon 1 of 6	ENSP00000384764.2	Q8IV42-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457082 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725000

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 86104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111278

Other (OTH) AF: 0.0000166 AC: 1 AN: 60204

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.5
DANN	Benign	0.74
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.046
Sift	Benign	0.22	T
Sift4G	Benign	0.19	T
Polyphen		0.0050	B
Vest4		0.11
MutPred		0.27		Gain of helix (P = 0.0199)
MVP		0.36
MPC		0.10
ClinPred		0.14	T
GERP RS		-2.5
PromoterAI		-0.037	Neutral
Varity_R		0.037
gMVP		0.50
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs983685436; hg19: chr10-124740039;