NM_001363531.2:c.215C>T

Variant names:

• chr10-122980694-C-T
• rs766987914
• NM_001363531.2:c.215C>T

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.215C>T​(p.Ala72Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,192,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/26 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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. A72E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: PSTK NM_001363531.2 missense, splice_region
• Scores: Splicing: ADA: 0.003423
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• 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=0.097510636).

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.215C>T	p.Ala72Val	missense splice_region	Exon 1 of 6	NP_001350460.1	H7BYY4
	PSTK	NM_153336.3		c.215C>T	p.Ala72Val	missense splice_region	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.215C>T	p.Ala72Val	missense splice_region	Exon 1 of 6	ENSP00000384653.3	H7BYY4
	PSTK	ENST00000368887.7	TSL:1	c.215C>T	p.Ala72Val	missense splice_region	Exon 1 of 7	ENSP00000357882.3	Q8IV42-1
	PSTK	ENST00000405485.2	TSL:2	c.215C>T	p.Ala72Val	missense splice_region	Exon 1 of 6	ENSP00000384764.2	Q8IV42-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00 AC: 0 AN: 175228 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000252 AC: 3 AN: 1192704 Hom.: 0 Cov.: 32 AF XY: 0.00000340 AC XY: 2 AN XY: 587450

African (AFR) AF: 0.00 AC: 0 AN: 24858

American (AMR) AF: 0.00 AC: 0 AN: 32916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16934

East Asian (EAS) AF: 0.00 AC: 0 AN: 15610

South Asian (SAS) AF: 0.00 AC: 0 AN: 78094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3256

European-Non Finnish (NFE) AF: 0.00000317 AC: 3 AN: 947370

Other (OTH) AF: 0.00 AC: 0 AN: 43858

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.000090	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	N
PhyloP100		0.075
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.018
Sift	Benign	0.28	T
Sift4G	Benign	0.28	T
Polyphen		0.42	B
Vest4		0.015
MutPred		0.29		Loss of loop (P = 0.0128)
MVP		0.51
MPC		0.11
ClinPred		0.22	T
GERP RS		-2.6
PromoterAI		-0.0052	Neutral
Varity_R		0.030
gMVP		0.17
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0034
dbscSNV1_RF	Benign	0.23
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.37		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs766987914; hg19: chr10-124740210; COSMIC: COSV64398371; COSMIC: COSV64398371;