chr15-64204453-AA-TG

Variant names:

• chr15-64204453-AA-TG
• NM_022048.5:c.986_987delTTinsCA
• CSNK1G1 p.Val329Ala

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_022048.5(CSNK1G1):​c.986_987delTTinsCA​(p.Val329Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in 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)
• Consequence: CSNK1G1 NM_022048.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.986_987delTTinsCA	p.Val329Ala	missense	N/A	NP_071331.2	Q9HCP0-1
	CSNK1G1	NM_001329605.2		c.986_987delTTinsCA	p.Val329Ala	missense	N/A	NP_001316534.1	U3KQB3
	CSNK1G1	NM_001329607.2		c.986_987delTTinsCA	p.Val329Ala	missense	N/A	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.986_987delTTinsCA	p.Val329Ala	missense	N/A	ENSP00000305777.7	Q9HCP0-1
	CSNK1G1	ENST00000607537.6	TSL:1	c.986_987delTTinsCA	p.Val329Ala	missense	N/A	ENSP00000475724.1	U3KQB3
	CSNK1G1	ENST00000561349.6	TSL:1	c.986_987delTTinsCA	p.Val329Ala	missense	N/A	ENSP00000476088.2	Q8IXA3

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-64496652;