3-184261246-G-T

Variant names:

• chr3-184261246-G-T
• rs760755093
• NM_033259.3:c.40C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033259.3(CAMK2N2):​c.40C>A​(p.Arg14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMK2N2 NM_033259.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 0 publications found

Genes affected

CAMK2N2 (HGNC:24197): (calcium/calmodulin dependent protein kinase II inhibitor 2) This gene encodes a protein that is highly similar to the rat CaM-KII inhibitory protein, an inhibitor of calcium/calmodulin-dependent protein kinase II (CAMKII). CAMKII regulates numerous physiological functions, including neuronal synaptic plasticity through the phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate (AMPA) receptors. Studies of the similar protein in rat suggest that this protein may function as a negative regulator of CaM-KII and may act to inhibit the phosphorylation of AMPA receptors. [provided by RefSeq, Jul 2008]

EEF1AKMT4-ECE2 (HGNC:53615): (EEF1AKMT4-ECE2 readthrough) This gene represents naturally occurring readthrough transcription between adjacent genes eukaryotic translation elongation factor 1 alpha lysine methyltransferase 4 (GeneID: 110599564) and endothelin converting enzyme 2 (GeneID:9718). The readthrough transcript representing this gene encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22033104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033259.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2N2	NM_033259.3	MANE Select	c.40C>A	p.Arg14Ser	missense	Exon 1 of 2	NP_150284.1	Q96S95
	EEF1AKMT4-ECE2	NM_014693.4		c.480+3490G>T		intron	N/A	NP_055508.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2N2	ENST00000296238.4	TSL:1 MANE Select	c.40C>A	p.Arg14Ser	missense	Exon 1 of 2	ENSP00000296238.3	Q96S95
	EEF1AKMT4-ECE2	ENST00000402825.7	TSL:1	c.480+3490G>T		intron	N/A	ENSP00000384223.3	P0DPD8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.028
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.73	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.92	T
PhyloP100		2.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.037
Sift	Benign	0.17	T
Sift4G	Benign	0.34	T
Polyphen		0.048	B
Vest4		0.25
MutPred		0.24		Loss of glycosylation at K11 (P = 0.08)
MVP		0.088
MPC		1.1
ClinPred		0.99	D
GERP RS		3.9
PromoterAI		-0.082	Neutral
Varity_R		0.28
gMVP		0.24
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs760755093; hg19: chr3-183979034;