Variant 2-168075126-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_013233.3(STK39):c.1195G>A(p.Ala399Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0126 in 1,614,172 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 13 hom., cov: 32)

Exomes 𝑓: 0.013 ( 148 hom. )

Consequence

STK39
NM_013233.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006496787).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0114 (1734/152290) while in subpopulation AMR AF= 0.0191 (292/15306). AF 95% confidence interval is 0.0173. There are 13 homozygotes in gnomad4. There are 831 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1734 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK39	NM_013233.3 linkuse as main transcript	c.1195G>A	p.Ala399Thr	missense_variant	11/18	ENST00000355999.5	NP_037365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK39	ENST00000355999.5 linkuse as main transcript	c.1195G>A	p.Ala399Thr	missense_variant	11/18	1	NM_013233.3	ENSP00000348278	P1	Q9UEW8-1
STK39	ENST00000487143.5 linkuse as main transcript	n.295G>A		non_coding_transcript_exon_variant	2/9	1
STK39	ENST00000697205.1 linkuse as main transcript	c.1195G>A	p.Ala399Thr	missense_variant	11/17			ENSP00000513185

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1735

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00331

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0115

AC:

2870

AN:

249496

Hom.:

AF XY:

0.0115

AC XY:

1557

AN XY:

135372

show subpopulations

Gnomad AFR exome

AF:

0.00207

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00356

Gnomad FIN exome

AF:

0.00761

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0127

AC:

18621

AN:

1461882

Hom.:

148

Cov.:

AF XY:

0.0126

AC XY:

9149

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.0153

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00349

Gnomad4 FIN exome

AF:

0.00889

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0114

AC:

1734

AN:

152290

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

831

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00330

Gnomad4 AMR

AF:

0.0191

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.0160

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0121

TwinsUK

AF:

0.0154

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00201

AC:

ESP6500EA

AF:

0.0144

AC:

120

ExAC

AF:

0.0108

AC:

1307

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0177

EpiControl

AF:

0.0161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.9

REVEL

Benign

0.18

Sift

Benign

0.054

Sift4G

Benign

0.17

Polyphen

0.60

Vest4

0.68

MPC

0.12

ClinPred

0.013

GERP RS

5.6

Varity_R

0.14

gMVP

0.56

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over