Genetic Variant STK17B:p.Pro282Ser (chr2-196137722-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004226.4(STK17B):c.844C>T(p.Pro282Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STK17B
NM_004226.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.91

Publications

0 publications found

Variant links:

Genes affected

STK17B (HGNC:11396): (serine/threonine kinase 17b) Enables ATP binding activity and protein serine/threonine kinase activity. Involved in intracellular signal transduction; positive regulation of fibroblast apoptotic process; and protein phosphorylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

STK17B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3981736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK17B	NM_004226.4 link	c.844C>T	p.Pro282Ser	missense_variant	Exon 8 of 8	ENST00000263955.9	NP_004217.1	O94768Q53QE7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK17B	ENST00000263955.9 link	c.844C>T	p.Pro282Ser	missense_variant	Exon 8 of 8	1	NM_004226.4	ENSP00000263955.4		O94768

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1448006

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32854

American (AMR)

AF:

0.00

AC:

AN:

42378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25680

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.0000238

AC:

AN:

84072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104936

Other (OTH)

AF:

0.00

AC:

AN:

59798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 18, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.844C>T (p.P282S) alteration is located in exon 8 (coding exon 7) of the STK17B gene. This alteration results from a C to T substitution at nucleotide position 844, causing the proline (P) at amino acid position 282 to be replaced by a serine (S). 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

0.29

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.2

M;M

PhyloP100

2.9

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.19

Sift

Benign

0.064

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.70

P;P

Vest4

0.42

MutPred

0.59

Loss of glycosylation at P282 (P = 0.0415);Loss of glycosylation at P282 (P = 0.0415);

MVP

0.65

MPC

1.3

ClinPred

0.77

GERP RS

4.8

Varity_R

0.14

gMVP

0.64

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over