rs145582574

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_173354.5(SIK1):c.1072C>G(p.Pro358Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 14 hom., cov: 0)

Exomes 𝑓: 0.022 ( 488 hom. )

Failed GnomAD Quality Control

Consequence

SIK1
NM_173354.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

SIK1 (HGNC:11142): (salt inducible kinase 1) This gene encodes a serine/threonine protein kinase that contains a ubiquitin-associated (UBA) domain. The encoded protein is a member of the adenosine monophosphate-activated kinase (AMPK) subfamily of kinases that play a role in conserved signal transduction pathways. A mutation in this gene is associated with early infantile epileptic encephalopathy 30. [provided by RefSeq, Nov 2016]

SIK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043595433).

BP6

Variant 21-43419906-G-C is Benign according to our data. Variant chr21-43419906-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 476075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43419906-G-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK1	NM_173354.5 link	c.1072C>G	p.Pro358Ala	missense_variant	Exon 9 of 14	ENST00000270162.8	NP_775490.2	P57059
SIK1	XM_011529474.3 link	c.972+328C>G		intron_variant	Intron 8 of 12		XP_011527776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK1	ENST00000270162.8 link	c.1072C>G	p.Pro358Ala	missense_variant	Exon 9 of 14	1	NM_173354.5	ENSP00000270162.6		P57059
SIK1	ENST00000644871.1 link	n.17C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

4704

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000867

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00794

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0517

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0208

GnomAD3 exomes

AF:

0.00244

AC:

558

AN:

228454

Hom.:

AF XY:

0.00235

AC XY:

292

AN XY:

124232

show subpopulations

Gnomad AFR exome

AF:

0.000436

Gnomad AMR exome

AF:

0.000367

Gnomad ASJ exome

AF:

0.00148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000348

Gnomad FIN exome

AF:

0.00365

Gnomad NFE exome

AF:

0.00426

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0219

AC:

1178

AN:

53800

Hom.:

488

Cov.:

AF XY:

0.0224

AC XY:

630

AN XY:

28152

show subpopulations

Gnomad4 AFR exome

AF:

0.00532

Gnomad4 AMR exome

AF:

0.00890

Gnomad4 ASJ exome

AF:

0.0140

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00279

Gnomad4 FIN exome

AF:

0.122

Gnomad4 NFE exome

AF:

0.0243

Gnomad4 OTH exome

AF:

0.0156

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00956

AC:

AN:

4706

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

AN XY:

2060

show subpopulations

Gnomad4 AFR

AF:

0.000865

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00794

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0517

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00287

Hom.:

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000913

AC:

ESP6500EA

AF:

0.00350

AC:

ExAC

AF:

0.00301

AC:

363

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Apr 26, 2017

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SIK1: BP4, BS2 -

Developmental and epileptic encephalopathy, 30

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.083

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.50

REVEL

Benign

0.076

Sift

Benign

0.26

Sift4G

Benign

0.74

Polyphen

0.0010

Vest4

0.17

MVP

0.32

MPC

0.18

ClinPred

0.0063

GERP RS

3.0

Varity_R

0.035

gMVP

0.15

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