Genetic Variant STK17B:p.Ile164Val (chr2-196143677-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_004226.4(STK17B):c.490A>G(p.Ile164Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000522 in 1,531,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

STK17B
NM_004226.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.14

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK17B	NM_004226.4 link	c.490A>G	p.Ile164Val	missense_variant	Exon 5 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.490A>G	p.Ile164Val	missense_variant	Exon 5 of 8	1	NM_004226.4	ENSP00000263955.4		O94768

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

197806

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000102

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:

0.00000363

AC:

AN:

1379254

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

684258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29762

American (AMR)

AF:

0.0000667

AC:

AN:

30004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22864

East Asian (EAS)

AF:

0.00

AC:

AN:

37526

South Asian (SAS)

AF:

0.00

AC:

AN:

72776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50860

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5276

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1073704

Other (OTH)

AF:

0.0000177

AC:

AN:

56482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.000197

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.490A>G (p.I164V) alteration is located in exon 5 (coding exon 4) of the STK17B gene. This alteration results from a A to G substitution at nucleotide position 490, causing the isoleucine (I) at amino acid position 164 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.0079

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.94

L;L

PhyloP100

5.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.18

Sift

Benign

0.061

T;T

Sift4G

Uncertain

0.041

D;D

Polyphen

0.53

P;P

Vest4

0.21

MutPred

0.85

Gain of ubiquitination at K160 (P = 0.0913);Gain of ubiquitination at K160 (P = 0.0913);

MVP

0.60

MPC

1.1

ClinPred

0.48

GERP RS

5.3

Varity_R

0.11

gMVP

0.44

Mutation Taster

=65/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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2-196143677-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over