dbSNP rs1135401818: CAMTA1:p.Arg955Trp (chr1-7677682-C-T) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate

The NM_015215.4(CAMTA1):c.2863C>T(p.Arg955Trp) variant causes a missense change. 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 Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CAMTA1
NM_015215.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.94

Publications

1 publications found

Variant links:

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]

CAMTA1 Gene-Disease associations (from GenCC):

cerebellar dysfunction with variable cognitive and behavioral abnormalities
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet

CAMTA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.838

PP5

Variant 1-7677682-C-T is Pathogenic according to our data. Variant chr1-7677682-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 431151.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015215.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CAMTA1	NM_015215.4	MANE Select	c.2863C>T	p.Arg955Trp	missense	Exon 11 of 23	NP_056030.1
CAMTA1	NM_001349614.1		c.-66C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 15	NP_001336543.1
CAMTA1	NM_001349617.1		c.-66C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 15	NP_001336546.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CAMTA1	ENST00000303635.12	TSL:1 MANE Select	c.2863C>T	p.Arg955Trp	missense	Exon 11 of 23	ENSP00000306522.6
CAMTA1	ENST00000476864.2	TSL:1	c.2863C>T	p.Arg955Trp	missense	Exon 11 of 22	ENSP00000452319.2
CAMTA1	ENST00000495233.6	TSL:1	n.*63C>T		non_coding_transcript_exon	Exon 2 of 14	ENSP00000451720.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cerebellar dysfunction with variable cognitive and behavioral abnormalities

Pathogenic:1

Jan 06, 2017

Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ASD with Intellectual disability

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.037

MetaRNN

Pathogenic

0.84

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

PhyloP100

4.9

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.91

MutPred

0.49

Gain of catalytic residue at A954 (P = 0.0219)

MVP

0.73

MPC

1.4

ClinPred

1.0

GERP RS

5.1

Varity_R

0.73

gMVP

0.79

Mutation Taster

=8/92

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over