2-44362120-C-G

Position:

• chr2-44362120-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024766.5(CAMKMT):​c.113C>G​(p.Ala38Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000756 in 1,322,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CAMKMT NM_024766.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12

Genes affected

CAMKMT (HGNC:26276): (calmodulin-lysine N-methyltransferase) This gene encodes a class I protein methyltransferase that acts in the formation of trimethyllysine in calmodulin. The protein contains a AdoMet-binding motif and may play a role in calcium-dependent signaling. [provided by RefSeq, Sep 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38400617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKMT	NM_024766.5	c.113C>G	p.Ala38Gly	missense_variant	1/11	ENST00000378494.8	NP_079042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKMT	ENST00000378494.8	c.113C>G	p.Ala38Gly	missense_variant	1/11	1	NM_024766.5	ENSP00000367755.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.56e-7 AC: 1 AN: 1322118 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 652702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000522

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: 0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.113C>G (p.A38G) alteration is located in exon 1 (coding exon 1) of the CAMKMT gene. This alteration results from a C to G substitution at nucleotide position 113, causing the alanine (A) at amino acid position 38 to be replaced by a glycine (G). 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	Benign	0.13
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	.;T;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.9	.;.;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.036	D;T;D;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		1.0, 0.99	.;.;D;D
Vest4		0.49
MutPred		0.41		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);
MVP		0.61
MPC		0.079
ClinPred		0.82	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.20
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs1048571888; hg19: chr2-44589259;