chr3-41224631-C-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM5PP2PP5
The NM_001904.4(CTNNB1):c.119C>T(p.Thr40Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T40A) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 32)
Consequence
CTNNB1
NM_001904.4 missense
NM_001904.4 missense
Scores
2
8
4
Clinical Significance
Conservation
PhyloP100: 6.00
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 Likely_pathogenic. Variant got 8 ACMG points.
PM1
In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 3 uncertain in NM_001904.4
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr3-41224630-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376237.Status of the report is no_assertion_criteria_provided, 0 stars.
PP2
Missense variant where missense usually causes diseases, CTNNB1
PP5
Variant 3-41224631-C-T is Pathogenic according to our data. Variant chr3-41224631-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376240.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTNNB1 | NM_001904.4 | c.119C>T | p.Thr40Ile | missense_variant | 3/15 | ENST00000349496.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTNNB1 | ENST00000349496.11 | c.119C>T | p.Thr40Ile | missense_variant | 3/15 | 1 | NM_001904.4 | 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
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
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
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
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
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
0.52, 0.51, 0.52, 0.51, 0.52
MutPred
Loss of glycosylation at T40 (P = 0.0071);.;Loss of glycosylation at T40 (P = 0.0071);.;Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);.;Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);.;.;Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);.;.;.;.;Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);.;Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);.;Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);.;Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);Loss of glycosylation at T40 (P = 0.0071);
MVP
0.55
MPC
1.4
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