chr21-43418451-G-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_173354.5(SIK1):c.1553C>T(p.Ala518Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 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. A518G) 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 -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIK1 | NM_173354.5 | c.1553C>T | p.Ala518Val | missense_variant | 12/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.1406C>T | p.Ala469Val | missense_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.1553C>T | p.Ala518Val | missense_variant | 12/14 | 1 | NM_173354.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 6Hom.: 0 Cov.: 0 FAILED QC
GnomAD3 exomes AF: 0.000329 AC: 80AN: 243384Hom.: 0 AF XY: 0.000354 AC XY: 47AN XY: 132654
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00104 AC: 10AN: 9576Hom.: 1 Cov.: 0 AF XY: 0.000801 AC XY: 4AN XY: 4994
GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 6Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 0
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 22, 2021 | 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
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | SIK1: BP4 - |
Developmental and epileptic encephalopathy, 30 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at