2-44372753-A-T

Position:

• chr2-44372753-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024766.5(CAMKMT):​c.176A>T​(p.His59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMKMT NM_024766.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMKMT	NM_024766.5	c.176A>T	p.His59Leu	missense_variant	2/11	ENST00000378494.8	NP_079042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMKMT	ENST00000378494.8	c.176A>T	p.His59Leu	missense_variant	2/11	1	NM_024766.5	ENSP00000367755	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Dec 21, 2022

The c.176A>T (p.H59L) alteration is located in exon 2 (coding exon 2) of the CAMKMT gene. This alteration results from a A to T substitution at nucleotide position 176, causing the histidine (H) at amino acid position 59 to be replaced by a leucine (L). 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	0.097
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.11	.;T;.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.073
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	.;.;L;L
MutationTaster	Benign	0.79	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.4	D;D;D;N
REVEL	Benign	0.059
Sift	Benign	0.045	D;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.76, 0.20	.;.;P;B
Vest4		0.57
MutPred		0.49		Gain of sheet (P = 0.0016);Gain of sheet (P = 0.0016);Gain of sheet (P = 0.0016);Gain of sheet (P = 0.0016);
MVP		0.63
MPC		0.092
ClinPred		0.42	T
GERP RS		2.0
Varity_R		0.088
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs945626575; hg19: chr2-44599892;