Variant chr2-196146004-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004226.4(STK17B):c.387G>C(p.Met129Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,052 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

STK17B
NM_004226.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

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 made for transcript

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=0.08289802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK17B	NM_004226.4 linkuse as main transcript	c.387G>C	p.Met129Ile	missense_variant	4/8	ENST00000263955.9	NP_004217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK17B	ENST00000263955.9 linkuse as main transcript	c.387G>C	p.Met129Ile	missense_variant	4/8	1	NM_004226.4	ENSP00000263955	P1
STK17B	ENST00000409228.5 linkuse as main transcript	c.387G>C	p.Met129Ile	missense_variant	4/8	1		ENSP00000386853	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454052

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723174

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.387G>C (p.M129I) alteration is located in exon 4 (coding exon 3) of the STK17B gene. This alteration results from a G to C substitution at nucleotide position 387, causing the methionine (M) at amino acid position 129 to be replaced by an isoleucine (I). 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

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.048

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.033

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.083

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.53

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.14

N;N

REVEL

Benign

0.042

Sift

Benign

0.37

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0010

B;B

Vest4

0.17

MutPred

0.30

Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);

MVP

0.45

MPC

0.49

ClinPred

0.16

GERP RS

5.0

Varity_R

0.20

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over