1-209609913-G-A

Position:

• chr1-209609913-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020439.3(CAMK1G):​c.811G>A​(p.Ala271Thr) 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. A271D) 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: 9.63

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]

CAMK1G (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK1G	NM_020439.3	c.811G>A	p.Ala271Thr	missense_variant	9/13	ENST00000361322.3	NP_065172.1
CAMK1G	XM_017001866.3	c.811G>A	p.Ala271Thr	missense_variant	9/13		XP_016857355.1
CAMK1G	XM_017001867.2	c.331G>A	p.Ala111Thr	missense_variant	6/10		XP_016857356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK1G	ENST00000361322.3	c.811G>A	p.Ala271Thr	missense_variant	9/13	1	NM_020439.3	ENSP00000354861.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 13, 2022

The c.811G>A (p.A271T) alteration is located in exon 9 (coding exon 8) of the CAMK1G gene. This alteration results from a G to A substitution at nucleotide position 811, causing the alanine (A) at amino acid position 271 to be replaced by a threonine (T). 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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		0.99	D;D
Vest4		0.89
MutPred		0.66		Gain of ubiquitination at K270 (P = 0.0666);Gain of ubiquitination at K270 (P = 0.0666);
MVP		0.56
MPC		1.9
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.58
gMVP		0.83

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-209783258;