rs55839518

Positions:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_015690.5(STK36):c.1158T>C(p.Asp386=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,613,450 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 17 hom. )

Consequence

STK36
NM_015690.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

STK36 (HGNC:17209): (serine/threonine kinase 36) This gene encodes a member of the serine/threonine kinase family of enzymes. This family member is similar to a Drosophila protein that plays a key role in the Hedgehog signaling pathway. This human protein is a positive regulator of the GLI zinc-finger transcription factors. Knockout studies of the homologous mouse gene suggest that defects in this human gene may lead to congenital hydrocephalus, possibly due to a functional defect in motile cilia. Because Hedgehog signaling is frequently activated in certain kinds of gastrointestinal cancers, it has been suggested that this gene is a target for the treatment of these cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

STK36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-218680624-T-C is Benign according to our data. Variant chr2-218680624-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 403499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218680624-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.32 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK36	NM_015690.5 linkuse as main transcript	c.1158T>C	p.Asp386=	synonymous_variant	10/27	ENST00000295709.8	NP_056505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK36	ENST00000295709.8 linkuse as main transcript	c.1158T>C	p.Asp386=	synonymous_variant	10/27	1	NM_015690.5	ENSP00000295709	P1	Q9NRP7-1
STK36	ENST00000392105.7 linkuse as main transcript	c.1158T>C	p.Asp386=	synonymous_variant	10/27	1		ENSP00000375954		Q9NRP7-2
STK36	ENST00000440309.5 linkuse as main transcript	c.1158T>C	p.Asp386=	synonymous_variant	10/27	5		ENSP00000394095	P1	Q9NRP7-1
STK36	ENST00000414413.5 linkuse as main transcript	c.54T>C	p.Asp18=	synonymous_variant, NMD_transcript_variant	2/6	5		ENSP00000406184

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

521

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00557

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00334

AC:

833

AN:

249402

Hom.:

AF XY:

0.00343

AC XY:

462

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.000623

Gnomad AMR exome

AF:

0.00334

Gnomad ASJ exome

AF:

0.00210

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000429

Gnomad FIN exome

AF:

0.00136

Gnomad NFE exome

AF:

0.00548

Gnomad OTH exome

AF:

0.00412

GnomAD4 exome

AF:

0.00451

AC:

6594

AN:

1461140

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

3267

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00360

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000488

Gnomad4 FIN exome

AF:

0.00182

Gnomad4 NFE exome

AF:

0.00533

Gnomad4 OTH exome

AF:

0.00447

GnomAD4 genome

AF:

0.00342

AC:

521

AN:

152310

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00557

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00395

Hom.:

Bravo

AF:

0.00368

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00742

EpiControl

AF:

0.00629

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	STK36: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant not in splice consensus -

STK36-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 06, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.32

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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