20-37802913-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030877.5(CTNNBL1):c.1078G>A(p.Ala360Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,858 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CTNNBL1 NM_030877.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.88

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNBL1	NM_030877.5	c.1078G>A	p.Ala360Thr	missense_variant	11/16	ENST00000361383.11
CTNNBL1	NM_001281495.2	c.997G>A	p.Ala333Thr	missense_variant	12/17
CTNNBL1	XM_024451947.2	c.997G>A	p.Ala333Thr	missense_variant	12/17
CTNNBL1	XM_011528917.3	c.748G>A	p.Ala250Thr	missense_variant	9/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.1078G>A	p.Ala360Thr	missense_variant	11/16	1	NM_030877.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727226

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2021

The c.1078G>A (p.A360T) alteration is located in exon 11 (coding exon 11) of the CTNNBL1 gene. This alteration results from a G to A substitution at nucleotide position 1078, causing the alanine (A) at amino acid position 360 to be replaced by a threonine (T). 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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;.;D;D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D
MetaSVM	Benign	-0.79	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.81	D
Sift4G	Benign	0.099	T;T;T;T;T;T
Polyphen		0.35, 0.24	.;.;B;.;B;.
Vest4		0.72
MutPred		0.77		.;.;Gain of loop (P = 0.0312);.;.;.;
MVP		0.51
MPC		0.69
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.50
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-36431315;