chr10-122980523-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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. P15L) 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

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=0.088288754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSTK	NM_001363531.2	c.44C>A	p.Pro15Gln	missense_variant	Exon 1 of 6	ENST00000406217.8	NP_001350460.1
PSTK	NM_153336.3	c.44C>A	p.Pro15Gln	missense_variant	Exon 1 of 7		NP_699167.2
PSTK	XM_017015641.3	c.44C>A	p.Pro15Gln	missense_variant	Exon 1 of 4		XP_016871130.1
PSTK	XR_001747018.2	n.123C>A		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	c.44C>A	p.Pro15Gln	missense_variant	Exon 1 of 6	5	NM_001363531.2	ENSP00000384653.3

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

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.41	.;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;.;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.39	N;.;N
REVEL	Benign	0.046
Sift	Benign	0.22	T;.;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0050	B;.;B
Vest4		0.11
MutPred		0.27		Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);
MVP		0.36
MPC		0.10
ClinPred		0.14	T
GERP RS		-2.5
Varity_R		0.037
gMVP		0.50

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: chr10-124740039;