rs759838082
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong
The NM_173354.5(SIK1):c.1064G>A(p.Arg355His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R355C) has been classified as Uncertain significance.
Frequency
Consequence
NM_173354.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.1064G>A | p.Arg355His | missense_variant | 9/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.972+320G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.1064G>A | p.Arg355His | missense_variant | 9/14 | 1 | NM_173354.5 | P1 | |
SIK1 | ENST00000644871.1 | n.9G>A | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 3464Hom.: 0 Cov.: 0 FAILED QC
GnomAD3 exomes AF: 0.000218 AC: 49AN: 225070Hom.: 0 AF XY: 0.000245 AC XY: 30AN XY: 122276
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000924 AC: 4AN: 43274Hom.: 1 Cov.: 0 AF XY: 0.0000438 AC XY: 1AN XY: 22846
GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 3464Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 1528
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 15, 2018 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | SIK1: BS1, BS2 - |
Developmental and epileptic encephalopathy, 30 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at