chr20-483965-T-A

Variant names:

• chr20-483965-T-A
• rs754115866
• NM_177559.3:c.1172A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_177559.3(CSNK2A1):​c.1172A>T​(p.Gln391Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSNK2A1 NM_177559.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the CSNK2A1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 28 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: 3.7123 (above the threshold of 3.09). Trascript score misZ: 5.3205 (above the threshold of 3.09). GenCC associations: The gene is linked to syndromic intellectual disability, Okur-Chung neurodevelopmental syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.1933771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2A1	NM_177559.3	c.1172A>T	p.Gln391Leu	missense_variant	Exon 14 of 14	ENST00000217244.9	NP_808227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK2A1	ENST00000217244.9	c.1172A>T	p.Gln391Leu	missense_variant	Exon 14 of 14	1	NM_177559.3	ENSP00000217244.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248938 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134774

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T;T;T;.;T;T;.;.;T;.;.;.;.;.;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.047
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	.;.;.;.;.;.;T;.;.;T;.;T;T;T;.;T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	N;N;N;.;N;N;.;.;N;.;.;.;.;.;N;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.56	.;.;.;.;N;.;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.24
Sift	Pathogenic	0.0	.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.
Sift4G	Pathogenic	0.0	.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.
Polyphen		0.27	B;B;B;.;B;B;.;.;B;.;.;.;.;.;B;B
Vest4		0.51
MutPred		0.28		Gain of stability (P = 0);Gain of stability (P = 0);Gain of stability (P = 0);.;Gain of stability (P = 0);Gain of stability (P = 0);.;.;Gain of stability (P = 0);.;.;.;.;.;Gain of stability (P = 0);Gain of stability (P = 0);
MVP		0.84
MPC		0.065
ClinPred		0.49	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs754115866; hg19: chr20-464609;