1-6825098-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP6

The NM_015215.4(CAMTA1):c.122A>G(p.His41Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,402,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CAMTA1 NM_015215.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.79

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CAMTA1
• BP6: Variant 1-6825098-A-G is Benign according to our data. Variant chr1-6825098-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 984541.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMTA1	NM_015215.4	c.122A>G	p.His41Arg	missense_variant	3/23	ENST00000303635.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMTA1	ENST00000303635.12	c.122A>G	p.His41Arg	missense_variant	3/23	1	NM_015215.4	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1402624 Hom.: 0 Cov.: 23 AF XY: 0.00000143 AC XY: 1 AN XY: 700372

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: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurodevelopmental abnormality Benign:1

Likely benign, no assertion criteria provided

clinical testing

Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine

Apr 03, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.021	T;.;.;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N;N;N;.
MutationTaster	Benign	0.95	D;D;D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.5	N;D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.99	D;.;.;.
Vest4		0.67
MutPred		0.25		Gain of solvent accessibility (P = 0.0074);Gain of solvent accessibility (P = 0.0074);Gain of solvent accessibility (P = 0.0074);.;
MVP		0.83
MPC		1.5
ClinPred		0.91	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.13
gMVP		0.30

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: rs1646960047; hg19: chr1-6885158;