10-12791169-C-G

Variant names:

• chr10-12791169-C-G
• NM_153498.4:c.577C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_153498.4(CAMK1D):​c.577C>G​(p.Leu193Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CAMK1D NM_153498.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.810
• 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: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.577C>G	p.Leu193Val	missense	Exon 6 of 11	NP_705718.1	Q8IU85-1
	CAMK1D	NM_020397.4		c.577C>G	p.Leu193Val	missense	Exon 6 of 10	NP_065130.1	Q5SQQ7
	CAMK1D	NM_001351032.2		c.286C>G	p.Leu96Val	missense	Exon 8 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.577C>G	p.Leu193Val	missense	Exon 6 of 11	ENSP00000478874.1	Q8IU85-1
	CAMK1D	ENST00000378845.5	TSL:1	c.577C>G	p.Leu193Val	missense	Exon 6 of 10	ENSP00000368122.1	Q8IU85-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461838 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.81
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.10	T
Polyphen		0.99	D
Vest4		0.75
MutPred		0.71		Loss of ubiquitination at K196 (P = 0.1166)
MVP		0.62
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.73
gMVP		0.68
Mutation Taster		=45/55	disease causing

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: chr10-12833168;