2-44362026-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024766.5(CAMKMT):c.19G>C(p.Asp7His) variant causes a missense change. The variant allele was found at a frequency of 0.000000791 in 1,264,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: CAMKMT NM_024766.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15900102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMKMT	NM_024766.5	c.19G>C	p.Asp7His	missense_variant	1/11	ENST00000378494.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMKMT	ENST00000378494.8	c.19G>C	p.Asp7His	missense_variant	1/11	1	NM_024766.5	P1
CAMKMT	ENST00000403853.7	c.19G>C	p.Asp7His	missense_variant	1/4	1
CAMKMT	ENST00000402247.5	c.19G>C	p.Asp7His	missense_variant	1/4	2
CAMKMT	ENST00000407131.5	c.19G>C	p.Asp7His	missense_variant	1/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.91e-7 AC: 1 AN: 1264768 Hom.: 0 Cov.: 31 AF XY: 0.00000162 AC XY: 1 AN XY: 617526

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: 9.78e-7

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

Dec 18, 2023

The c.19G>C (p.D7H) alteration is located in exon 1 (coding exon 1) of the CAMKMT gene. This alteration results from a G to C substitution at nucleotide position 19, causing the aspartic acid (D) at amino acid position 7 to be replaced by a histidine (H). 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	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	17
Dann	Uncertain	0.98
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.62	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.082	T;T;T;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.90, 0.26	.;.;P;B
Vest4		0.31
MutPred		0.20		Gain of MoRF binding (P = 0.0312);Gain of MoRF binding (P = 0.0312);Gain of MoRF binding (P = 0.0312);Gain of MoRF binding (P = 0.0312);
MVP		0.36
MPC		0.45
ClinPred		0.32	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.090
gMVP		0.38

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: chr2-44589165;