chr3-41224073-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM1PP2BP4
The NM_001904.4(CTNNB1):c.5C>G(p.Ala2Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
CTNNB1
NM_001904.4 missense
NM_001904.4 missense
Scores
1
4
9
Clinical Significance
Conservation
PhyloP100: 4.59
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 2 ACMG points.
PM1
?
In a modified_residue N-acetylalanine (size 0) in uniprot entity CTNB1_HUMAN
PP2
?
Missense variant where missense usually causes diseases, CTNNB1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3628875).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTNNB1 | NM_001904.4 | c.5C>G | p.Ala2Gly | missense_variant | 2/15 | ENST00000349496.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNNB1 | ENST00000349496.11 | c.5C>G | p.Ala2Gly | missense_variant | 2/15 | 1 | NM_001904.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152148Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251364Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135852
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461482Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 727068
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74326
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1362552). This variant has not been reported in the literature in individuals affected with CTNNB1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 2 of the CTNNB1 protein (p.Ala2Gly). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
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
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
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
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
Polyphen
P;P;P;P;P;P;P;P;P;P;P;P;P;P;.;.;.;P;.;P;P;P;.;P;P;P;P;P;P
Vest4
0.46, 0.45, 0.45, 0.49
MutPred
Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);Loss of glycosylation at T3 (P = 0.1324);
MVP
0.51
MPC
1.2
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at