20-486400-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_177559.3(CSNK2A1):c.1036G>A(p.Val346Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,472 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
CSNK2A1
NM_177559.3 missense
NM_177559.3 missense
Scores
1
3
10
Clinical Significance
Conservation
PhyloP100: 5.64
Genes affected
CSNK2A1 (HGNC:2457): (casein kinase 2 alpha 1) Casein kinase II is a serine/threonine protein kinase that phosphorylates acidic proteins such as casein. It is involved in various cellular processes, including cell cycle control, apoptosis, and circadian rhythm. The kinase exists as a tetramer and is composed of an alpha, an alpha-prime, and two beta subunits. The alpha subunits contain the catalytic activity while the beta subunits undergo autophosphorylation. The protein encoded by this gene represents the alpha subunit. Multiple transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Apr 2018]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, CSNK2A1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1708082).
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSNK2A1 | NM_177559.3 | c.1036G>A | p.Val346Ile | missense_variant | 13/14 | ENST00000217244.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSNK2A1 | ENST00000217244.9 | c.1036G>A | p.Val346Ile | missense_variant | 13/14 | 1 | NM_177559.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000462 AC: 7AN: 151666Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251390Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135876
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461806Hom.: 0 Cov.: 30 AF XY: 0.0000399 AC XY: 29AN XY: 727210
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GnomAD4 genome ? AF: 0.0000462 AC: 7AN: 151666Hom.: 0 Cov.: 31 AF XY: 0.0000405 AC XY: 3AN XY: 73988
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T;T;.;T;T;.;.;.;T;.;.;.;.;.;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.;.;.;N;N;.;.;.;N;.;.;.;.;.;N;N
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Polyphen
B;B;B;.;.;.;B;B;.;.;.;B;.;.;.;.;.;B;B
Vest4
0.62, 0.63
MutPred
Loss of catalytic residue at V346 (P = 0.0295);Loss of catalytic residue at V346 (P = 0.0295);Loss of catalytic residue at V346 (P = 0.0295);.;Loss of catalytic residue at V346 (P = 0.0295);.;Loss of catalytic residue at V346 (P = 0.0295);Loss of catalytic residue at V346 (P = 0.0295);.;.;Loss of catalytic residue at V346 (P = 0.0295);Loss of catalytic residue at V346 (P = 0.0295);.;.;.;.;.;Loss of catalytic residue at V346 (P = 0.0295);Loss of catalytic residue at V346 (P = 0.0295);
MVP
0.77
MPC
0.045
ClinPred
T
GERP RS
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gMVP
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at