chr10-12769680-ATC-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 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 id is 3376508.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK1D	NM_153498.4	c.450_451delCT	p.Leu151ValfsTer6	frameshift_variant	Exon 5 of 11	ENST00000619168.5	NP_705718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK1D	ENST00000619168.5	c.450_451delCT	p.Leu151ValfsTer6	frameshift_variant	Exon 5 of 11	1	NM_153498.4	ENSP00000478874.1
CAMK1D	ENST00000378845.5	c.450_451delCT	p.Leu151ValfsTer6	frameshift_variant	Exon 5 of 10	1		ENSP00000368122.1

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

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability Pathogenic:1

Nov 11, 2024

Genologica Medica

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This de novo detected variant c.450_451delC (p.Leu151fs) detected in Heterozygosity in exon 5 of the CAMK1D gene causes the loss of 2 nucleotides of the c.DNA (NM_153498.4) and, consequently, gives rise to a break in the open reading frame. The protein consequence involves a change in the amino acid sequence downstream of Leucine (Leu) located at position 151 and, probably, the appearance of a premature stop codon (STOP). This variant is expected to result in an absent or non-functional protein product. This variant has not been reported so far in the control population database (GnomAD - not frequent). This variant has not been reported so far in the ClinVar database nor, to our knowledge, has it been published in the scientific literature. Based on the criteria described, this alteration is classified as a Probably Pathogenic variant. -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-12811679;