5-111224586-G-A

Variant names:

• chr5-111224586-G-A
• NM_001744.6:c.103G>A

Variant summary

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

The NM_001744.6(CAMK4):​c.103G>A​(p.Asp35Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CAMK4 NM_001744.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81
• Publications: 0 publications found

Genes affected

CAMK4 (HGNC:1464): (calcium/calmodulin dependent protein kinase IV) The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. [provided by RefSeq, Jul 2008]

CAMK4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

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=0.22252202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001744.6. 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
	CAMK4	NM_001744.6	MANE Select	c.103G>A	p.Asp35Asn	missense	Exon 1 of 11	NP_001735.1	Q16566
	CAMK4	NM_001323374.2		c.103G>A	p.Asp35Asn	missense	Exon 2 of 12	NP_001310303.1	Q16566
	CAMK4	NM_001323375.2		c.103G>A	p.Asp35Asn	missense	Exon 2 of 12	NP_001310304.1	Q16566

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK4	ENST00000282356.9	TSL:1 MANE Select	c.103G>A	p.Asp35Asn	missense	Exon 1 of 11	ENSP00000282356.4	Q16566
	CAMK4	ENST00000512453.5	TSL:1	c.103G>A	p.Asp35Asn	missense	Exon 2 of 12	ENSP00000422634.1	Q16566
	CAMK4	ENST00000515231.5	TSL:1	n.103G>A		non_coding_transcript_exon	Exon 1 of 9	ENSP00000424912.1	D6RCD6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Benign	0.33
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.092
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.90	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Benign	0.086	T
Sift4G	Uncertain	0.015	D
Polyphen		0.047	B
Vest4		0.37
MutPred		0.34		Loss of phosphorylation at S37 (P = 0.1165)
MVP		0.74
MPC		0.72
ClinPred		0.87	D
GERP RS		4.2
PromoterAI		0.034	Neutral
Varity_R		0.32
gMVP		0.19
Mutation Taster		=85/15	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

hg19: chr5-110560284; COSMIC: COSV56680559;