chr1-209599996-G-C

Position:

• chr1-209599996-G-C

Variant summary

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

The NM_020439.3(CAMK1G):​c.106G>C​(p.Glu36Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAMK1G NM_020439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.64

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK1G	NM_020439.3	c.106G>C	p.Glu36Gln	missense_variant	3/13	ENST00000361322.3	NP_065172.1
CAMK1G	XM_017001866.3	c.106G>C	p.Glu36Gln	missense_variant	3/13		XP_016857355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK1G	ENST00000361322.3	c.106G>C	p.Glu36Gln	missense_variant	3/13	1	NM_020439.3	ENSP00000354861.2
CAMK1G	ENST00000009105.5	c.106G>C	p.Glu36Gln	missense_variant	3/13	2		ENSP00000009105.1
CAMK1G	ENST00000423146.5	c.106G>C	p.Glu36Gln	missense_variant	3/8	3		ENSP00000392173.1
CAMK1G	ENST00000651530.1	c.-183G>C		5_prime_UTR_variant	4/14			ENSP00000498823.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Nov 02, 2023

The c.106G>C (p.E36Q) alteration is located in exon 3 (coding exon 2) of the CAMK1G gene. This alteration results from a G to C substitution at nucleotide position 106, causing the glutamic acid (E) at amino acid position 36 to be replaced by a glutamine (Q). 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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	-0.015	N;.;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.4	N;D;N
REVEL	Uncertain	0.42
Sift	Benign	0.056	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.92	P;.;P
Vest4		0.78
MutPred		0.61		Gain of MoRF binding (P = 0.0486);Gain of MoRF binding (P = 0.0486);Gain of MoRF binding (P = 0.0486);
MVP		0.72
MPC		0.21
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.37
gMVP		0.60

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: chr1-209773341;