15-64204454-A-T

Variant names:

• chr15-64204454-A-T
• NM_022048.5:c.986T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022048.5(CSNK1G1):​c.986T>A​(p.Val329Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,440,996 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V329I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: CSNK1G1 NM_022048.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

Genes affected

CSNK1G1 (HGNC:2454): (casein kinase 1 gamma 1) This gene encodes a member of the casein kinase I gene family. This family is comprised of serine/threonine kinases that phosphorylate acidic proteins such as caseins. The encoded kinase plays a role in cell cycle checkpoint arrest in response to stalled replication forks by phosphorylating Claspin. A mutation in this gene may be associated with non-syndromic early-onset epilepsy (NSEOE). [provided by RefSeq, Jul 2016]

ENSG00000259316 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1G1	NM_022048.5	c.986T>A	p.Val329Asp	missense_variant	Exon 9 of 12	ENST00000303052.13	NP_071331.2
CSNK1G1	NM_001329605.2	c.986T>A	p.Val329Asp	missense_variant	Exon 9 of 13		NP_001316534.1
CSNK1G1	NM_001329607.2	c.986T>A	p.Val329Asp	missense_variant	Exon 9 of 12		NP_001316536.1
CSNK1G1	NM_001329606.2	c.986T>A	p.Val329Asp	missense_variant	Exon 9 of 12		NP_001316535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1G1	ENST00000303052.13	c.986T>A	p.Val329Asp	missense_variant	Exon 9 of 12	1	NM_022048.5	ENSP00000305777.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1440996 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 716296

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: 0.00000452

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.52	D;T;T;.;T;T;T;T;T;.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;D;.;D;D;D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.86	L;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.7	D;.;.;.;.;.;.;.;.;.;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0040	D;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.086	T;D;T;T;D;D;D;D;D;D;D
Polyphen		0.11	B;.;B;.;.;.;.;.;.;.;.
Vest4		0.74
MutPred		0.47		Gain of catalytic residue at V329 (P = 0.0799);Gain of catalytic residue at V329 (P = 0.0799);Gain of catalytic residue at V329 (P = 0.0799);Gain of catalytic residue at V329 (P = 0.0799);Gain of catalytic residue at V329 (P = 0.0799);Gain of catalytic residue at V329 (P = 0.0799);.;.;.;Gain of catalytic residue at V329 (P = 0.0799);.;
MVP		0.51
MPC		1.1
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-64496653;