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GeneBe

1-6825205-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2

The NM_015215.4(CAMTA1):c.229A>G(p.Asn77Asp) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N77K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CAMTA1
NM_015215.4 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1
In a DNA_binding_region CG-1 (size 125) in uniprot entity CMTA1_HUMAN there are 8 pathogenic changes around while only 1 benign (89%) in NM_015215.4
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, CAMTA1

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CAMTA1NM_015215.4 linkuse as main transcriptc.229A>G p.Asn77Asp missense_variant 3/23 ENST00000303635.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CAMTA1ENST00000303635.12 linkuse as main transcriptc.229A>G p.Asn77Asp missense_variant 3/231 NM_015215.4 P2Q9Y6Y1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1411308
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
703832
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cerebellar dysfunction with variable cognitive and behavioral abnormalities Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testing;provider interpretationGeisinger Autism and Developmental Medicine Institute, Geisinger Health SystemMay 25, 2017This is a 26 year old female with generalized anxiety disorder, depression, obsessive compulsive disorder, learning disability, speech delay hypernasal speech, hypersomnia, spastic diplegia, and scoliosis. There is no history of ataxia. There is a maternal history of depression and anxiety and paternal history of dyslexia. This p.N77D variant is absent from the gnomAD database. Computational prediction models are inconsistent. Whole exome sequencing identified 2 additional variants of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Benign
-0.0042
T
BayesDel_noAF
Benign
-0.24
Cadd
Pathogenic
28
Dann
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.;.;.
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Benign
0.0075
T
MetaRNN
Uncertain
0.71
D;D;D;D
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.1
M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-3.0
D;D;D;D
REVEL
Uncertain
0.33
Sift
Uncertain
0.021
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;.;.;.
Vest4
0.86
MutPred
0.50
Gain of phosphorylation at T76 (P = 0.0877);Gain of phosphorylation at T76 (P = 0.0877);Gain of phosphorylation at T76 (P = 0.0877);.;
MVP
0.73
MPC
0.76
ClinPred
0.95
D
GERP RS
6.0
Varity_R
0.29
gMVP
0.57

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.

Other links and lift over

dbSNP: rs1557636777; hg19: chr1-6885265; API