10-12769680-ATC-A

Variant names:

• chr10-12769680-ATC-A
• NM_153498.4:c.450_451delCT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_153498.4(CAMK1D):​c.450_451delCT​(p.Leu151ValfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAMK1D NM_153498.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.21
• Publications: 0 publications found

Genes affected

CAMK1D (HGNC:19341): (calcium/calmodulin dependent protein kinase ID) This gene is a member of the calcium/calmodulin-dependent protein kinase 1 family, a subfamily of the serine/threonine kinases. The encoded protein is a component of the calcium-regulated calmodulin-dependent protein kinase cascade. It has been associated with multiple processes including regulation of granulocyte function, activation of CREB-dependent gene transcription, aldosterone synthesis, differentiation and activation of neutrophil cells, and apoptosis of erythroleukemia cells. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-12769680-ATC-A is Pathogenic according to our data. Variant chr10-12769680-ATC-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3376508.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153498.4. 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
	CAMK1D	NM_153498.4	MANE Select	c.450_451delCT	p.Leu151ValfsTer6	frameshift	Exon 5 of 11	NP_705718.1	Q8IU85-1
	CAMK1D	NM_020397.4		c.450_451delCT	p.Leu151ValfsTer6	frameshift	Exon 5 of 10	NP_065130.1	Q5SQQ7
	CAMK1D	NM_001351032.2		c.159_160delCT	p.Leu54ValfsTer6	frameshift	Exon 7 of 12	NP_001337961.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK1D	ENST00000619168.5	TSL:1 MANE Select	c.450_451delCT	p.Leu151ValfsTer6	frameshift	Exon 5 of 11	ENSP00000478874.1	Q8IU85-1
	CAMK1D	ENST00000378845.5	TSL:1	c.450_451delCT	p.Leu151ValfsTer6	frameshift	Exon 5 of 10	ENSP00000368122.1	Q8IU85-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

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

Other links and lift over

hg19: chr10-12811679;