Variant X-132072828-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_016542.4(STK26):c.1042C>A(p.Gln348Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,208,989 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000071 ( 0 hom. 28 hem. )

Consequence

STK26
NM_016542.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Variant links:

Genes affected

STK26 (HGNC:18174): (serine/threonine kinase 26) The product of this gene is a member of the GCK group III family of kinases, which are a subset of the Ste20-like kinases. The encoded protein contains an amino-terminal kinase domain, and a carboxy-terminal regulatory domain that mediates homodimerization. The protein kinase localizes to the Golgi apparatus and is specifically activated by binding to the Golgi matrix protein GM130. It is also cleaved by caspase-3 in vitro, and may function in the apoptotic pathway. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

STK26 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=0.09874573).

BS2

High Hemizygotes in GnomAdExome4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK26	NM_016542.4 linkuse as main transcript	c.1042C>A	p.Gln348Lys	missense_variant	10/12	ENST00000394334.7	NP_057626.2	Q9P289-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK26	ENST00000394334.7 linkuse as main transcript	c.1042C>A	p.Gln348Lys	missense_variant	10/12	1	NM_016542.4	ENSP00000377867.2		Q9P289-1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112450

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34626

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000944

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000602

AC:

AN:

182735

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

67463

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

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:

0.0000737

Gnomad OTH exome

AF:

0.000444

GnomAD4 exome

AF:

0.0000711

AC:

AN:

1096539

Hom.:

Cov.:

AF XY:

0.0000773

AC XY:

AN XY:

362203

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

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:

0.0000856

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112450

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34626

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000944

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.00

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 29, 2024

The c.1042C>A (p.Q348K) alteration is located in exon 10 (coding exon 9) of the STK26 gene. This alteration results from a C to A substitution at nucleotide position 1042, causing the glutamine (Q) at amino acid position 348 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

0.060

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.059

T;.;.;.

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.099

T;T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.40

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.38

T;T;T;T

Sift4G

Benign

0.95

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.086

MutPred

0.46

.;Gain of ubiquitination at Q370 (P = 0.0109);.;.;

MVP

0.44

MPC

0.81

ClinPred

0.068

GERP RS

4.9

Varity_R

0.42

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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