rs28931588
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP5_Moderate
The NM_001904.4(CTNNB1):c.94G>A(p.Asp32Asn) 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
CTNNB1
NM_001904.4 missense
NM_001904.4 missense
Scores
10
4
5
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
CTNNB1 (HGNC:2514): (catenin beta 1) The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the CTNNB1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 43 curated pathogenic missense variants (we use a threshold of 10). The gene has 15 curated benign missense variants. Gene score misZ: 3.846 (above the threshold of 3.09). Trascript score misZ: 5.712 (above the threshold of 3.09). GenCC associations: The gene is linked to severe intellectual disability-progressive spastic diplegia syndrome, exudative vitreoretinopathy, exudative vitreoretinopathy 7.
PP5
Variant 3-41224606-G-A is Pathogenic according to our data. Variant chr3-41224606-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 376228.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CTNNB1 | NM_001904.4 | c.94G>A | p.Asp32Asn | missense_variant | Exon 3 of 15 | ENST00000349496.11 | NP_001895.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Juvenile nasopharyngeal angiofibroma Pathogenic:1
Jul 30, 2021
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant was identified in 23% of reads, consistent with somatic origin. To our knowledge, this variant has not previously been reported in juvenile nasopharyngeal angiofibroma (JNA), but this is an oncogenic variant found in multiple tumor types (COSMIC and cBioPortal Databases). -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;T;D;T;D;D;D;D;D;T;D;D;.;T;D;D;D;T;.;T;T;D;D;.;.;.;D;T;.;D;D;T;D;.;D;T;D;D;D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
.;D;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;D;.;.;.;.;T;D;D;.;.;D;.;.;.;.;D;.;D;.;.;.;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.;M;M;M;M;M;.;M;M;.;.;M;M;M;.;.;.;.;M;M;.;.;.;M;.;.;M;M;.;M;.;M;.;M;M;M;M;M
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
.;D;.;.;D;.;.;.;D;.;D;D;.;.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D
REVEL
Uncertain
Sift
Pathogenic
.;D;.;.;D;.;.;.;D;.;D;D;.;.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D
Sift4G
Pathogenic
.;D;.;.;D;.;.;.;D;.;D;D;.;.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D
Polyphen
D;.;D;.;D;D;D;D;D;.;D;D;.;.;D;D;D;.;.;.;.;D;D;.;.;.;D;.;.;D;D;.;D;.;D;.;D;D;D;D;D
Vest4
0.79, 0.77, 0.77, 0.79, 0.82
MutPred
Gain of MoRF binding (P = 0.0548);.;Gain of MoRF binding (P = 0.0548);.;Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);.;Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);.;.;Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);.;.;.;.;Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);.;Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);.;Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);.;Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);Gain of MoRF binding (P = 0.0548);
MVP
0.79
MPC
1.9
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