rs373872652

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_173354.5(SIK1):​c.2049G>A​(p.Pro683Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.000044 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

SIK1
NM_173354.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -3.21
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 21-43417045-C-T is Benign according to our data. Variant chr21-43417045-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 476095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43417045-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-3.21 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SIK1NM_173354.5 linkuse as main transcriptc.2049G>A p.Pro683Pro synonymous_variant 14/14 ENST00000270162.8 NP_775490.2 P57059
SIK1XM_011529474.3 linkuse as main transcriptc.1902G>A p.Pro634Pro synonymous_variant 13/13 XP_011527776.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SIK1ENST00000270162.8 linkuse as main transcriptc.2049G>A p.Pro683Pro synonymous_variant 14/141 NM_173354.5 ENSP00000270162.6 P57059

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD3 exomes
AF:
0.000689
AC:
42
AN:
60930
Hom.:
1
AF XY:
0.000693
AC XY:
23
AN XY:
33168
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000298
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000923
Gnomad SAS exome
AF:
0.00285
Gnomad FIN exome
AF:
0.00193
Gnomad NFE exome
AF:
0.000336
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000443
AC:
2
AN:
45192
Hom.:
1
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
23320
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.0000689
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
0
Alfa
AF:
0.00289
Hom.:
0
Asia WGS
AF:
0.000578
AC:
2
AN:
3474

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
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 17, 2016This 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. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2024SIK1: BP4, BP7 -
Developmental and epileptic encephalopathy, 30 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 11, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.051
DANN
Benign
0.54

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.

Other links and lift over

dbSNP: rs373872652; hg19: chr21-44836925; API