rs35596465
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_173354.5(SIK1):c.2174C>T(p.Ala725Val) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A725T) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.051 ( 17 hom., cov: 0)
Exomes 𝑓: 0.012 ( 231 hom. )
Failed GnomAD Quality Control
Consequence
SIK1
NM_173354.5 missense
NM_173354.5 missense
Scores
3
5
10
Clinical Significance
Conservation
PhyloP100: 8.45
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0021226406).
BP6
?
Variant 21-43416920-G-A is Benign according to our data. Variant chr21-43416920-G-A is described in ClinVar as [Benign]. Clinvar id is 476101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.2174C>T | p.Ala725Val | missense_variant | 14/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.2027C>T | p.Ala676Val | missense_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.2174C>T | p.Ala725Val | missense_variant | 14/14 | 1 | NM_173354.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 95AN: 1852Hom.: 17 Cov.: 0 FAILED QC
GnomAD3 genomes
?
AF:
AC:
95
AN:
1852
Hom.:
Cov.:
0
FAILED QC
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00306 AC: 429AN: 140164Hom.: 6 AF XY: 0.00240 AC XY: 183AN XY: 76330
GnomAD3 exomes
AF:
AC:
429
AN:
140164
Hom.:
AF XY:
AC XY:
183
AN XY:
76330
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0116 AC: 573AN: 49194Hom.: 231 Cov.: 0 AF XY: 0.0109 AC XY: 275AN XY: 25230
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
573
AN:
49194
Hom.:
Cov.:
0
AF XY:
AC XY:
275
AN XY:
25230
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0510 AC: 95AN: 1864Hom.: 17 Cov.: 0 AF XY: 0.0566 AC XY: 43AN XY: 760
GnomAD4 genome
?
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
95
AN:
1864
Hom.:
Cov.:
0
AF XY:
AC XY:
43
AN XY:
760
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
171
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
274
Asia WGS
AF:
AC:
6
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 29, 2016 | 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. - |
Developmental and epileptic encephalopathy, 30 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at