NM_022048.5:c.985G>A

Variant names:

• chr15-64204455-C-T
• rs55699712
• NM_022048.5:c.985G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_022048.5(CSNK1G1):​c.985G>A​(p.Val329Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0082 in 1,585,338 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V329A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0059 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0084 (68 hom.)
• Consequence: CSNK1G1 NM_022048.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.02
• Publications: 14 publications found

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]

CSNK1G1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000259316 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007820845).
• BP6: Variant 15-64204455-C-T is Benign according to our data. Variant chr15-64204455-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2645442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 883 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022048.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1G1	NM_022048.5	MANE Select	c.985G>A	p.Val329Ile	missense	Exon 9 of 12	NP_071331.2	Q9HCP0-1
	CSNK1G1	NM_001329605.2		c.985G>A	p.Val329Ile	missense	Exon 9 of 13	NP_001316534.1	U3KQB3
	CSNK1G1	NM_001329607.2		c.985G>A	p.Val329Ile	missense	Exon 9 of 12	NP_001316536.1	Q8IXA3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1G1	ENST00000303052.13	TSL:1 MANE Select	c.985G>A	p.Val329Ile	missense	Exon 9 of 12	ENSP00000305777.7	Q9HCP0-1
	CSNK1G1	ENST00000607537.6	TSL:1	c.985G>A	p.Val329Ile	missense	Exon 9 of 13	ENSP00000475724.1	U3KQB3
	CSNK1G1	ENST00000561349.6	TSL:1	c.985G>A	p.Val329Ile	missense	Exon 8 of 11	ENSP00000476088.2	Q8IXA3

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 884 AN: 150314 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00139

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.00595

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000634

Gnomad FIN AF: 0.00220

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00946

Gnomad OTH AF: 0.00969

GnomAD2 exomes AF: 0.00602 AC: 1389 AN: 230696 AF XY: 0.00589

Gnomad AFR exome AF: 0.00128

Gnomad AMR exome AF: 0.00470

Gnomad ASJ exome AF: 0.00656

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00185

Gnomad NFE exome AF: 0.00964

Gnomad OTH exome AF: 0.00926

GnomAD4 exome AF: 0.00845 AC: 12119 AN: 1434956 Hom.: 68 Cov.: 33 AF XY: 0.00819 AC XY: 5842 AN XY: 713228

African (AFR) AF: 0.00116 AC: 37 AN: 31764

American (AMR) AF: 0.00483 AC: 188 AN: 38946

Ashkenazi Jewish (ASJ) AF: 0.00636 AC: 160 AN: 25152

East Asian (EAS) AF: 0.00 AC: 0 AN: 39196

South Asian (SAS) AF: 0.00201 AC: 160 AN: 79768

European-Finnish (FIN) AF: 0.00208 AC: 110 AN: 52884

Middle Eastern (MID) AF: 0.00410 AC: 23 AN: 5610

European-Non Finnish (NFE) AF: 0.00993 AC: 10944 AN: 1102436

Other (OTH) AF: 0.00840 AC: 497 AN: 59200

GnomAD4 genome AF: 0.00587 AC: 883 AN: 150382 Hom.: 5 Cov.: 31 AF XY: 0.00563 AC XY: 412 AN XY: 73232

African (AFR) AF: 0.00139 AC: 57 AN: 41004

American (AMR) AF: 0.00595 AC: 90 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.000636 AC: 3 AN: 4718

European-Finnish (FIN) AF: 0.00220 AC: 22 AN: 10020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00944 AC: 639 AN: 67670

Other (OTH) AF: 0.00962 AC: 20 AN: 2080

Alfa AF: 0.00817 Hom.: 17

Bravo AF: 0.00635

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0103 AC: 89

ExAC AF: 0.00604 AC: 733

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.62	N
PhyloP100		5.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.082
Sift	Benign	0.41	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.32
MVP		0.35
MPC		0.38
ClinPred		0.011	T
GERP RS		5.5
PromoterAI		0.039	Neutral
Varity_R		0.086
gMVP		0.36
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs55699712; hg19: chr15-64496654; COSMIC: COSV57311677; COSMIC: COSV57311677;