20-37859951-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_030877.5(CTNNBL1):āc.1445A>Gā(p.Tyr482Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
CTNNBL1
NM_030877.5 missense
NM_030877.5 missense
Scores
13
5
1
Clinical Significance
Conservation
PhyloP100: 9.27
Genes affected
CTNNBL1 (HGNC:15879): (catenin beta like 1) The protein encoded by this gene is a component of the pre-mRNA-processing factor 19-cell division cycle 5-like (PRP19-CDC5L) protein complex, which activates pre-mRNA splicing and is an integral part of the spliceosome. The encoded protein is also a nuclear localization sequence binding protein, and binds to activation-induced deaminase and is important for antibody diversification. This gene may also be associated with the development of obesity. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on the X chromosome. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.906
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTNNBL1 | NM_030877.5 | c.1445A>G | p.Tyr482Cys | missense_variant | 14/16 | ENST00000361383.11 | NP_110517.2 | |
CTNNBL1 | NM_001281495.2 | c.1364A>G | p.Tyr455Cys | missense_variant | 15/17 | NP_001268424.1 | ||
CTNNBL1 | XM_024451947.2 | c.1364A>G | p.Tyr455Cys | missense_variant | 15/17 | XP_024307715.1 | ||
CTNNBL1 | XM_011528917.3 | c.1115A>G | p.Tyr372Cys | missense_variant | 12/14 | XP_011527219.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTNNBL1 | ENST00000361383.11 | c.1445A>G | p.Tyr482Cys | missense_variant | 14/16 | 1 | NM_030877.5 | ENSP00000355050.6 | ||
CTNNBL1 | ENST00000628103.2 | c.1364A>G | p.Tyr455Cys | missense_variant | 15/17 | 2 | ENSP00000487198.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461842Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727218
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74290
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 19, 2023 | The c.1445A>G (p.Y482C) alteration is located in exon 14 (coding exon 14) of the CTNNBL1 gene. This alteration results from a A to G substitution at nucleotide position 1445, causing the tyrosine (Y) at amino acid position 482 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;.;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
.;.;M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;D;.;D;D
REVEL
Pathogenic
Sift
Pathogenic
.;D;D;.;D;D
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;D;.
Vest4
MutPred
0.69
.;.;Gain of catalytic residue at L483 (P = 0.1024);.;.;.;
MVP
MPC
1.5
ClinPred
D
GERP RS
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gMVP
Splicing
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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