Variant X-132054721-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016542.4(STK26):c.133C>T(p.Arg45Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00547 in 1,209,396 control chromosomes in the GnomAD database, including 14 homozygotes. There are 2,176 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0046 ( 1 hom., 159 hem., cov: 23)

Exomes 𝑓: 0.0056 ( 13 hom. 2017 hem. )

Consequence

STK26
NM_016542.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.94

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00829038).

BP6

Variant X-132054721-C-T is Benign according to our data. Variant chrX-132054721-C-T is described in ClinVar as [Benign]. Clinvar id is 733537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 159 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK26	NM_016542.4 linkuse as main transcript	c.133C>T	p.Arg45Cys	missense_variant	3/12	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.133C>T	p.Arg45Cys	missense_variant	3/12	1	NM_016542.4	ENSP00000377867.2		Q9P289-1

Frequencies

GnomAD3 genomes

AF:

0.00465

AC:

519

AN:

111586

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

159

AN XY:

33788

show subpopulations

Gnomad AFR

AF:

0.000718

Gnomad AMI

AF:

0.00585

Gnomad AMR

AF:

0.00561

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000372

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.0168

Gnomad NFE

AF:

0.00623

Gnomad OTH

AF:

0.00668

GnomAD3 exomes

AF:

0.00549

AC:

1005

AN:

182974

Hom.:

AF XY:

0.00567

AC XY:

383

AN XY:

67568

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.00322

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000316

Gnomad FIN exome

AF:

0.00945

Gnomad NFE exome

AF:

0.00741

Gnomad OTH exome

AF:

0.00820

GnomAD4 exome

AF:

0.00556

AC:

6101

AN:

1097754

Hom.:

Cov.:

AF XY:

0.00555

AC XY:

2017

AN XY:

363178

show subpopulations

Gnomad4 AFR exome

AF:

0.000493

Gnomad4 AMR exome

AF:

0.00378

Gnomad4 ASJ exome

AF:

0.0142

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000462

Gnomad4 FIN exome

AF:

0.00805

Gnomad4 NFE exome

AF:

0.00588

Gnomad4 OTH exome

AF:

0.00682

GnomAD4 genome

AF:

0.00462

AC:

516

AN:

111642

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

159

AN XY:

33854

show subpopulations

Gnomad4 AFR

AF:

0.000716

Gnomad4 AMR

AF:

0.00551

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000372

Gnomad4 FIN

AF:

0.00885

Gnomad4 NFE

AF:

0.00620

Gnomad4 OTH

AF:

0.00660

Alfa

AF:

0.00663

Hom.:

286

Bravo

AF:

0.00421

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00381

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00595

AC:

ExAC

AF:

0.00593

AC:

720

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;T;.

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D;D

MetaRNN

Benign

0.0083

T;T;T;T

MetaSVM

Benign

-0.70

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-6.5

D;D;D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Benign

0.074

T;T;T;T

Polyphen

0.21

B;B;B;B

Vest4

0.41

MVP

0.80

MPC

1.9

ClinPred

0.063

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.85

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