Variant 2-168247354-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013233.3(STK39):c.82C>G(p.Pro28Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 146,056 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: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STK39
NM_013233.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.204

Variant links:

Genes affected

STK39 (HGNC:17717): (serine/threonine kinase 39) This gene encodes a serine/threonine kinase that is thought to function in the cellular stress response pathway. The kinase is activated in response to hypotonic stress, leading to phosphorylation of several cation-chloride-coupled cotransporters. The catalytically active kinase specifically activates the p38 MAP kinase pathway, and its interaction with p38 decreases upon cellular stress, suggesting that this kinase may serve as an intermediate in the response to cellular stress. [provided by RefSeq, Jul 2008]

STK39 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05006233).

BS2

High AC in GnomAd at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK39	NM_013233.3 linkuse as main transcript	c.82C>G	p.Pro28Ala	missense_variant	1/18	ENST00000355999.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK39	ENST00000355999.5 linkuse as main transcript	c.82C>G	p.Pro28Ala	missense_variant	1/18	1	NM_013233.3	P1	Q9UEW8-1
STK39	ENST00000697205.1 linkuse as main transcript	c.82C>G	p.Pro28Ala	missense_variant	1/17

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

145948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00469

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000109

AC:

AN:

910260

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

425750

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:

0.00504

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000247

Gnomad4 OTH exome

AF:

0.000187

GnomAD4 genome

AF:

0.000151

AC:

AN:

146056

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

AN XY:

71122

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00469

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000683

AC:

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 05, 2023

The c.82C>G (p.P28A) alteration is located in exon 1 (coding exon 1) of the STK39 gene. This alteration results from a C to G substitution at nucleotide position 82, causing the proline (P) at amino acid position 28 to be replaced by an alanine (A). 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

0.063

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Benign

0.25

DEOGEN2

Benign

0.097

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.29

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.75

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.67

REVEL

Benign

0.14

Sift

Benign

0.80

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.22

MutPred

0.39

Loss of glycosylation at P28 (P = 0.0094);

MVP

0.51

MPC

1.1

ClinPred

0.032

GERP RS

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.049

gMVP

0.24

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