rs991922432

Variant names:

• chr5-111224604-G-A
• rs991922432
• NM_001744.6:c.121G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-111224604-G-A
• chr5-111224604-G-T

Variant summary

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

The NM_001744.6(CAMK4):​c.121G>A​(p.Ala41Thr) 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. 13/21 in silico tools predict 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. A41S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMK4 NM_001744.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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]

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=0.09804064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK4	NM_001744.6	c.121G>A	p.Ala41Thr	missense_variant	Exon 1 of 11	ENST00000282356.9	NP_001735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK4	ENST00000282356.9	c.121G>A	p.Ala41Thr	missense_variant	Exon 1 of 11	1	NM_001744.6	ENSP00000282356.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0098	T;T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.70	T;.;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	.;N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.96	N;N;N
REVEL	Benign	0.093
Sift	Benign	0.48	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.0050	.;B;B
Vest4		0.11, 0.049
MutPred		0.25		Gain of phosphorylation at A41 (P = 0.0558);Gain of phosphorylation at A41 (P = 0.0558);Gain of phosphorylation at A41 (P = 0.0558);
MVP		0.57
MPC		0.71
ClinPred		0.20	T
GERP RS		1.0
Varity_R		0.071
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs991922432; hg19: chr5-110560302;