NM_020439.3:c.812C>A

Variant names:

• chr1-209609914-C-A
• NM_020439.3:c.812C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_020439.3(CAMK1G):​c.812C>A​(p.Ala271Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A271T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMK1G NM_020439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.62
• Publications: 0 publications found

Genes affected

CAMK1G (HGNC:14585): (calcium/calmodulin dependent protein kinase IG) Predicted to enable calmodulin binding activity and calmodulin-dependent protein kinase activity. Predicted to be involved in peptidyl-serine phosphorylation. Predicted to be located in endomembrane system. Predicted to be part of calcium- and calmodulin-dependent protein kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.946

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020439.3. 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
	CAMK1G	NM_020439.3	MANE Select	c.812C>A	p.Ala271Asp	missense	Exon 9 of 13	NP_065172.1	Q96NX5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK1G	ENST00000361322.3	TSL:1 MANE Select	c.812C>A	p.Ala271Asp	missense	Exon 9 of 13	ENSP00000354861.2	Q96NX5-1
	CAMK1G	ENST00000009105.5	TSL:2	c.812C>A	p.Ala271Asp	missense	Exon 9 of 13	ENSP00000009105.1	Q96NX5-1
	CAMK1G	ENST00000900039.1		c.812C>A	p.Ala271Asp	missense	Exon 9 of 13	ENSP00000570098.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.61
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.80		Gain of ubiquitination at K270 (P = 0.043)
MVP		0.81
MPC		2.3
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.96
gMVP		0.98
Mutation Taster		=12/88	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr1-209783259;