Variant chr20-484049-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_ModerateBS2

The NM_177559.3(CSNK2A1):c.1088C>A(p.Pro363His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,424 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P363S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CSNK2A1
NM_177559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.03

Variant links:

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]

CSNK2A1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CSNK2A1. . Gene score misZ 3.7123 (greater than the threshold 3.09). Trascript score misZ 5.3205 (greater than threshold 3.09). GenCC has associacion of gene with syndromic intellectual disability, Okur-Chung neurodevelopmental syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.25187397).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK2A1	NM_177559.3 linkuse as main transcript	c.1088C>A	p.Pro363His	missense_variant	14/14	ENST00000217244.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK2A1	ENST00000217244.9 linkuse as main transcript	c.1088C>A	p.Pro363His	missense_variant	14/14	1	NM_177559.3	P1	P68400-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458424

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725548

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Okur-Chung neurodevelopmental syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Oct 03, 2019

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

T;T;T;.;T;T;.;.;T;.;.;.;.;.;T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.88

.;.;.;.;.;.;D;.;.;D;.;D;D;D;.;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.25

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.69

N;N;N;.;N;N;.;.;N;.;.;.;.;.;N;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.28

.;.;.;.;N;.;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.19

Sift

Uncertain

0.0030

.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.

Sift4G

Uncertain

0.036

.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.

Polyphen

0.21

B;B;B;.;B;B;.;.;B;.;.;.;.;.;B;B

Vest4

0.32

MutPred

0.13

Loss of glycosylation at P363 (P = 0.062);Loss of glycosylation at P363 (P = 0.062);Loss of glycosylation at P363 (P = 0.062);.;Loss of glycosylation at P363 (P = 0.062);Loss of glycosylation at P363 (P = 0.062);.;.;Loss of glycosylation at P363 (P = 0.062);.;.;.;.;.;Loss of glycosylation at P363 (P = 0.062);Loss of glycosylation at P363 (P = 0.062);

MVP

0.64

MPC

0.15

ClinPred

0.48

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.28

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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