Variant 1-209605574-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020439.3(CAMK1G):c.335G>T(p.Arg112Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R112Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CAMK1G
NM_020439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.335G>T	p.Arg112Leu	missense_variant	5/13	ENST00000361322.3	NP_065172.1	Q96NX5-1
CAMK1G	XM_017001867.2 linkuse as main transcript	c.-146G>T		5_prime_UTR_premature_start_codon_gain_variant	2/10		XP_016857356.1
CAMK1G	XM_017001866.3 linkuse as main transcript	c.335G>T	p.Arg112Leu	missense_variant	5/13		XP_016857355.1	Q96NX5-1
CAMK1G	XM_017001867.2 linkuse as main transcript	c.-146G>T		5_prime_UTR_variant	2/10		XP_016857356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAMK1G	ENST00000361322.3 linkuse as main transcript	c.335G>T	p.Arg112Leu	missense_variant	5/13	1	NM_020439.3	ENSP00000354861.2	Q96NX5-1
CAMK1G	ENST00000009105.5 linkuse as main transcript	c.335G>T	p.Arg112Leu	missense_variant	5/13	2		ENSP00000009105.1	Q96NX5-1
CAMK1G	ENST00000651530.1 linkuse as main transcript	c.47G>T	p.Arg16Leu	missense_variant	6/14			ENSP00000498823.1	A0A494C109
CAMK1G	ENST00000423146.5 linkuse as main transcript	c.335G>T	p.Arg112Leu	missense_variant	5/8	3		ENSP00000392173.1	C9IYV2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251340

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.335G>T (p.R112L) alteration is located in exon 5 (coding exon 4) of the CAMK1G gene. This alteration results from a G to T substitution at nucleotide position 335, causing the arginine (R) at amino acid position 112 to be replaced by a leucine (L). 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

0.75

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.4

L;.;L

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.2

D;D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.49

MutPred

0.59

Loss of catalytic residue at R112 (P = 0.0936);Loss of catalytic residue at R112 (P = 0.0936);Loss of catalytic residue at R112 (P = 0.0936);

MVP

0.82

MPC

2.1

ClinPred

1.0

GERP RS

5.3

Varity_R

0.75

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over