chr1-6825205-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
NM_015215.4 missense
Scores
6
7
6
Clinical Significance
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]
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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 |
---|---|---|---|---|---|---|---|
CAMTA1 | NM_015215.4 | c.229A>G | p.Asn77Asp | missense_variant | 3/23 | ENST00000303635.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAMTA1 | ENST00000303635.12 | c.229A>G | p.Asn77Asp | missense_variant | 3/23 | 1 | NM_015215.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1411308Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 703832
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1411308
Hom.:
Cov.:
24
AF XY:
AC XY:
0
AN XY:
703832
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
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 submitter | clinical testing;provider interpretation | Geisinger Autism and Developmental Medicine Institute, Geisinger Health System | May 25, 2017 | This 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;.;.;.
Vest4
MutPred
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
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at