chr10-12791169-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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

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 Likely_benign. Variant got -3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK1D	NM_153498.4	c.577C>G	p.Leu193Val	missense_variant	Exon 6 of 11	ENST00000619168.5	NP_705718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK1D	ENST00000619168.5	c.577C>G	p.Leu193Val	missense_variant	Exon 6 of 11	1	NM_153498.4	ENSP00000478874.1
CAMK1D	ENST00000378845.5	c.577C>G	p.Leu193Val	missense_variant	Exon 6 of 10	1		ENSP00000368122.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.577C>G (p.L193V) alteration is located in exon 6 (coding exon 6) of the CAMK1D gene. This alteration results from a C to G substitution at nucleotide position 577, causing the leucine (L) at amino acid position 193 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.0	.;D;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	.;D;.
Sift4G	Benign	0.10	T;T;T
Polyphen		0.99	D;.;.
Vest4		0.75
MutPred		0.71		Loss of ubiquitination at K196 (P = 0.1166);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

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: chr10-12833168;