Variant 20-2103006-C-T 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_080836.4(STK35):c.533C>T(p.Ala178Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000789 in 1,267,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

STK35
NM_080836.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.109

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 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=0.08277291).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK35	NM_080836.4 linkuse as main transcript	c.533C>T	p.Ala178Val	missense_variant	2/4	ENST00000381482.8	NP_543026.2
STK35	XM_011529174.4 linkuse as main transcript	c.533C>T	p.Ala178Val	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.533C>T	p.Ala178Val	missense_variant	2/4	5	NM_080836.4	ENSP00000370891	P1
STK35	ENST00000493263.1 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant, NMD_transcript_variant	1/4	1		ENSP00000426612

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000338

AC:

AN:

29628

Hom.:

AF XY:

0.0000560

AC XY:

AN XY:

17858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000225

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

7.89e-7

AC:

AN:

1267922

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

621890

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000660

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Apr 07, 2023

The c.533C>T (p.A178V) alteration is located in exon 2 (coding exon 2) of the STK35 gene. This alteration results from a C to T substitution at nucleotide position 533, causing the alanine (A) at amino acid position 178 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

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0062

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.47

REVEL

Benign

0.067

Sift

Benign

0.12

Sift4G

Benign

0.088

Polyphen

0.0

Vest4

0.084

MutPred

0.24

Gain of catalytic residue at A178 (P = 0.0135);

MVP

0.14

MPC

1.1

ClinPred

0.076

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.066

gMVP

0.35

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