Genetic Variant CAMK1D:p.Ala33Thr (chr10-12553229-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_153498.4(CAMK1D):c.97G>A(p.Ala33Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,794 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: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CAMK1D
NM_153498.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.58

Publications

0 publications found

Variant links:

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]

CAMK1D links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK1D	NM_153498.4 link	c.97G>A	p.Ala33Thr	missense_variant	Exon 2 of 11	ENST00000619168.5	NP_705718.1	Q8IU85-1Q5SQQ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CAMK1D	ENST00000619168.5 link	c.97G>A	p.Ala33Thr	missense_variant	Exon 2 of 11	1	NM_153498.4	ENSP00000478874.1	Q8IU85-1
CAMK1D	ENST00000378845.5 link	c.97G>A	p.Ala33Thr	missense_variant	Exon 2 of 10	1		ENSP00000368122.1	Q8IU85-2
CAMK1D	ENST00000487696.1 link	n.260-113507G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111938

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 29, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.97G>A (p.A33T) alteration is located in exon 2 (coding exon 2) of the CAMK1D gene. This alteration results from a G to A substitution at nucleotide position 97, causing the alanine (A) at amino acid position 33 to be replaced by a threonine (T). 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

0.051

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.65

N;N

PhyloP100

9.6

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.5

.;D

REVEL

Benign

0.29

Sift

Benign

0.082

.;T

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;.

Vest4

0.77

MutPred

0.58

Gain of phosphorylation at A33 (P = 0.0654);Gain of phosphorylation at A33 (P = 0.0654);

MVP

0.57

ClinPred

0.99

GERP RS

5.1

Varity_R

0.63

gMVP

0.70

Mutation Taster

=35/65

disease causing

(source)

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

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10-12553229-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over