NM_001904.4:c.337C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001904.4(CTNNB1):​c.337C>A​(p.Gln113Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q113R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CTNNB1
NM_001904.4 missense

Scores

5
11
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91

Publications

0 publications found
Variant links:
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]
CTNNB1 Gene-Disease associations (from GenCC):
  • exudative vitreoretinopathy
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
  • severe intellectual disability-progressive spastic diplegia syndrome
    Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Illumina, G2P, Ambry Genetics
  • exudative vitreoretinopathy 7
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTNNB1NM_001904.4 linkc.337C>A p.Gln113Lys missense_variant Exon 4 of 15 ENST00000349496.11 NP_001895.1 P35222A0A024R2Q3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTNNB1ENST00000349496.11 linkc.337C>A p.Gln113Lys missense_variant Exon 4 of 15 1 NM_001904.4 ENSP00000344456.5 P35222
CTNNB1ENST00000645982.1 linkc.337C>A p.Gln113Lys missense_variant Exon 4 of 16 ENSP00000494845.1 P35222
CTNNB1ENST00000715152.1 linkn.337C>A non_coding_transcript_exon_variant Exon 4 of 16 ENSP00000520353.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461810
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727206
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33474
American (AMR)
AF:
0.00
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111954
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.71
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.87
D;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
0.60
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.98
.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;D;D;.;.;D;.;.;.;.;D;.;D;.;.;.;.;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.68
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.48
T
MutationAssessor
Uncertain
2.6
M;M;.;M;M;M;M;M;.;M;M;.;M;M;M;.;.;.;.;M;M;.;.;M;.;.;M;M;.;M;.;M;.;M;M;M;M;M
PhyloP100
7.9
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-2.8
.;.;.;D;.;.;.;D;.;D;D;.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
REVEL
Uncertain
0.31
Sift
Uncertain
0.0050
.;.;.;D;.;.;.;D;.;D;D;.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G
Uncertain
0.023
.;.;.;D;.;.;.;D;.;D;D;.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Polyphen
0.90
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
0.72, 0.73, 0.73, 0.73, 0.71
MutPred
0.45
Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);.;Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);.;Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);.;Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);.;.;.;.;Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);.;Gain of ubiquitination at Q113 (P = 0.0085);.;Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);.;Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);.;Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);Gain of ubiquitination at Q113 (P = 0.0085);
MVP
0.85
MPC
1.9
ClinPred
0.86
D
GERP RS
5.4
Varity_R
0.64
gMVP
0.80
Mutation Taster
=36/64
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1553630279; hg19: chr3-41266540; API