NM_030877.5:c.88C>T

Variant names:

• chr20-37732936-C-T
• rs202016331
• NM_030877.5:c.88C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030877.5(CTNNBL1):​c.88C>T​(p.Arg30Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,712 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: CTNNBL1 NM_030877.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26534265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.88C>T	p.Arg30Trp	missense_variant	Exon 2 of 16	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.7C>T	p.Arg3Trp	missense_variant	Exon 3 of 17		NP_001268424.1
CTNNBL1	XM_024451947.2	c.7C>T	p.Arg3Trp	missense_variant	Exon 3 of 17		XP_024307715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.88C>T	p.Arg30Trp	missense_variant	Exon 2 of 16	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.7C>T	p.Arg3Trp	missense_variant	Exon 3 of 17	2		ENSP00000487198.1
CTNNBL1	ENST00000447935.3	c.7C>T	p.Arg3Trp	missense_variant	Exon 3 of 7	5		ENSP00000394464.1
CTNNBL1	ENST00000621317.4	c.88C>T	p.Arg30Trp	missense_variant	Exon 2 of 17	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461712 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000355 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.88C>T (p.R30W) alteration is located in exon 2 (coding exon 2) of the CTNNBL1 gene. This alteration results from a C to T substitution at nucleotide position 88, causing the arginine (R) at amino acid position 30 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	.;.;T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T;T;T;T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	.;.;L;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.8	.;D;N;D;.
REVEL	Benign	0.11
Sift	Uncertain	0.0010	.;D;D;D;.
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		0.99, 1.0	.;.;D;D;.
Vest4		0.58
MutPred		0.21		Loss of solvent accessibility (P = 0.0509);.;Loss of solvent accessibility (P = 0.0509);.;.;
MVP		0.53
MPC		0.78
ClinPred		0.97	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs202016331; hg19: chr20-36361338; COSMIC: COSV63744911;