1-6825130-T-A

Variant names:

• chr1-6825130-T-A
• rs879255532
• NM_015215.4:c.154T>A

Variant summary

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

The NM_015215.4(CAMTA1):​c.154T>A​(p.Phe52Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAMTA1 NM_015215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMTA1	NM_015215.4	c.154T>A	p.Phe52Ile	missense_variant	Exon 3 of 23	ENST00000303635.12	NP_056030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMTA1	ENST00000303635.12	c.154T>A	p.Phe52Ile	missense_variant	Exon 3 of 23	1	NM_015215.4	ENSP00000306522.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457730 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725180

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cerebellar dysfunction with variable cognitive and behavioral abnormalities Uncertain:1

Apr 27, 2016

Center of Genomic medicine, Geneva, University Hospital of Geneva

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant in CAMTA1 was found in combination with an another pathogenic variant in CTNNB1 a patient with severe mental retardation, ataxia, microcephaly and epilepsy -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T;.;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.0053	T
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.4	N;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Benign	0.27	T;D;D;D
Polyphen		0.80	P;.;.;.
Vest4		0.77
MutPred		0.34		Gain of catalytic residue at L57 (P = 0.0233);Gain of catalytic residue at L57 (P = 0.0233);Gain of catalytic residue at L57 (P = 0.0233);.;
MVP		0.66
MPC		1.6
ClinPred		0.96	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.64

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: rs879255532; hg19: chr1-6885190;