1-6825140-A-G

Position:

• chr1-6825140-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_015215.4(CAMTA1):​c.164A>G​(p.Lys55Arg) 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: 32)
• Consequence: CAMTA1 NM_015215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.16

Genes affected

CAMTA1 (HGNC:18806): (calmodulin binding transcription activator 1) The protein encoded by this gene contains a CG1 DNA-binding domain, a transcription factor immunoglobulin domain, ankyrin repeats, and calmodulin-binding IQ motifs. The encoded protein is thought to be a transcription factor and may be a tumor suppressor. However, a translocation event is sometimes observed between this gene and the WWTR1 gene, with the resulting WWTR1-CAMTA1 oncoprotein leading to epithelioid hemangioendothelioma, a malignant vascular cancer. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CAMTA1. . Gene score misZ 3.2619 (greater than the threshold 3.09). Trascript score misZ 4.755 (greater than threshold 3.09). GenCC has associacion of gene with cerebellar dysfunction with variable cognitive and behavioral abnormalities.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMTA1	NM_015215.4	c.164A>G	p.Lys55Arg	missense_variant	3/23	ENST00000303635.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMTA1	ENST00000303635.12	c.164A>G	p.Lys55Arg	missense_variant	3/23	1	NM_015215.4	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 09, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with CAMTA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 55 of the CAMTA1 protein (p.Lys55Arg). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.021	T;.;.;.
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.0034	T
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	L;L;L;.
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.4	N;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.012	D;D;D;D
Sift4G	Uncertain	0.034	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.62
MutPred		0.27		Loss of methylation at K55 (P = 0.0122);Loss of methylation at K55 (P = 0.0122);Loss of methylation at K55 (P = 0.0122);.;
MVP		0.67
MPC		1.2
ClinPred		0.91	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.36

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: chr1-6885200;