Variant chr21-43416837-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_173354.5(SIK1):c.2257G>T(p.Ala753Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 0)

Consequence

SIK1
NM_173354.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0640

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009072959).

BP6

Variant 21-43416837-C-A is Benign according to our data. Variant chr21-43416837-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3162243.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIK1	NM_173354.5 linkuse as main transcript	c.2257G>T	p.Ala753Ser	missense_variant	14/14	ENST00000270162.8	NP_775490.2	P57059
SIK1	XM_011529474.3 linkuse as main transcript	c.2110G>T	p.Ala704Ser	missense_variant	13/13		XP_011527776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIK1	ENST00000270162.8 linkuse as main transcript	c.2257G>T	p.Ala753Ser	missense_variant	14/14	1	NM_173354.5	ENSP00000270162.6		P57059

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000121

AC:

AN:

238690

Hom.:

AF XY:

0.000137

AC XY:

AN XY:

130918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.000861

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

This alteration is classified as likely 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.0

DANN

Benign

0.66

DEOGEN2

Benign

0.071

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.44

M_CAP

Benign

0.015

MetaRNN

Benign

0.0091

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.12

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.17

REVEL

Benign

0.086

Sift

Benign

1.0

Sift4G

Benign

0.78

Polyphen

0.0010

Vest4

0.042

MutPred

0.21

Gain of sheet (P = 0.0266);

MVP

0.26

MPC

0.12

ClinPred

0.0046

GERP RS

-1.1

Varity_R

0.037

gMVP

0.23

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