rs121913394
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP2PP5BP4
The ENST00000349496.11(CTNNB1):c.37G>A(p.Ala13Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
CTNNB1
ENST00000349496.11 missense
ENST00000349496.11 missense
Scores
3
5
11
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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CTNNB1. . Gene score misZ 3.846 (greater than the threshold 3.09). Trascript score misZ 5.712 (greater than threshold 3.09). GenCC has associacion of gene with severe intellectual disability-progressive spastic diplegia syndrome, exudative vitreoretinopathy, exudative vitreoretinopathy 7.
PP5
Variant 3-41224549-G-A is Pathogenic according to our data. Variant chr3-41224549-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376223.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.28936157). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTNNB1 | NM_001904.4 | c.37G>A | p.Ala13Thr | missense_variant | 3/15 | ENST00000349496.11 | NP_001895.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTNNB1 | ENST00000349496.11 | c.37G>A | p.Ala13Thr | missense_variant | 3/15 | 1 | NM_001904.4 | ENSP00000344456 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Melanoma Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | Jul 14, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
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
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;D;.;.;.;.;T;D;D;.;.;D;.;.;.;.;D;.;D;.;.;.;.;D
M_CAP
Benign
T
MetaRNN
Benign
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
Benign
N;.;N;.;N;N;N;N;N;.;N;N;.;.;N;N;N;.;.;.;.;N;N;.;.;.;N;.;.;N;N;.;N;.;N;.;N;N;N;N;N
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;.;.;N;.;D;.;N;.;N;N;.;.;N;.;.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;N
REVEL
Benign
Sift
Uncertain
.;D;.;.;T;.;.;.;T;.;T;T;.;.;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;T
Sift4G
Pathogenic
.;D;.;.;T;.;.;.;T;.;T;T;.;.;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;T
Polyphen
B;.;B;.;B;B;B;B;B;.;B;B;.;.;B;B;B;.;.;.;.;B;B;.;.;.;B;.;.;B;B;.;B;.;B;.;B;B;B;B;B
Vest4
0.60, 0.61, 0.61, 0.60
MutPred
Gain of glycosylation at A13 (P = 0.0062);.;Gain of glycosylation at A13 (P = 0.0062);.;Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);.;Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);.;.;Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);.;.;.;.;Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);.;Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);.;Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);.;Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);Gain of glycosylation at A13 (P = 0.0062);
MVP
0.84
MPC
1.1
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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