Variant chr20-2102907-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_080836.4(STK35):c.434C>A(p.Thr145Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,561,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

STK35
NM_080836.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

STK35 (HGNC:16254): (serine/threonine kinase 35) The protein encoded by this gene is a kinase that is predominantly found in the nucleus. However, it can interact with PDLIM1/CLP-36 in the cytoplasm and localize to actin stress fibers. The encoded protein may be a regulator of actin stress fibers in nonmuscle cells. [provided by RefSeq, Jul 2008]

STK35 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18142578).

BS2

High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK35	NM_080836.4 linkuse as main transcript	c.434C>A	p.Thr145Lys	missense_variant	2/4	ENST00000381482.8	NP_543026.2
STK35	XM_011529174.4 linkuse as main transcript	c.434C>A	p.Thr145Lys	missense_variant	2/3		XP_011527476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK35	ENST00000381482.8 linkuse as main transcript	c.434C>A	p.Thr145Lys	missense_variant	2/4	5	NM_080836.4	ENSP00000370891	P1
STK35	ENST00000493263.1 linkuse as main transcript	c.17C>A	p.Thr6Lys	missense_variant, NMD_transcript_variant	1/4	1		ENSP00000426612

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152158

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:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000114

AC:

AN:

176192

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

99442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000836

Gnomad NFE exome

AF:

0.000138

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.000112

AC:

158

AN:

1409604

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

700168

show subpopulations

Gnomad4 AFR exome

AF:

0.0000330

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000616

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.0000512

GnomAD4 genome

AF:

0.000118

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74326

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:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000695

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

Jan 25, 2023

The c.434C>A (p.T145K) alteration is located in exon 2 (coding exon 2) of the STK35 gene. This alteration results from a C to A substitution at nucleotide position 434, causing the threonine (T) at amino acid position 145 to be replaced by a lysine (K). 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

0.22

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.53

D;N

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-0.36

REVEL

Benign

0.16

Sift

Uncertain

0.014

Sift4G

Uncertain

0.0070

Polyphen

0.90

Vest4

0.42

MutPred

0.26

Loss of phosphorylation at T145 (P = 0.0018);

MVP

0.52

MPC

1.3

ClinPred

0.15

GERP RS

5.1

Varity_R

0.31

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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