rs430554
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_173354.5(SIK1):c.1844C>T(p.Ala615Val) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A615T) has been classified as Likely benign.
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.1844C>T | p.Ala615Val | missense_variant | 13/14 | ENST00000270162.8 | |
SIK1 | XM_011529474.3 | c.1697C>T | p.Ala566Val | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIK1 | ENST00000270162.8 | c.1844C>T | p.Ala615Val | missense_variant | 13/14 | 1 | NM_173354.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 2139AN: 37422Hom.: 495 Cov.: 0 FAILED QC
GnomAD3 exomes AF: 0.888 AC: 192033AN: 216326Hom.: 85333 AF XY: 0.887 AC XY: 104913AN XY: 118324
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0649 AC: 21219AN: 327096Hom.: 9830 Cov.: 0 AF XY: 0.0680 AC XY: 10998AN XY: 161722
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0573 AC: 2147AN: 37466Hom.: 498 Cov.: 0 AF XY: 0.0563 AC XY: 984AN XY: 17480
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 30 Benign:3
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 20, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 30, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 31, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 93. Only high quality variants are reported. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 31, 2015 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at