chr20-37803039-G-A

Position:

• chr20-37803039-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030877.5(CTNNBL1):​c.1204G>A​(p.Glu402Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNBL1 NM_030877.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNBL1	NM_030877.5	c.1204G>A	p.Glu402Lys	missense_variant	11/16	ENST00000361383.11
CTNNBL1	NM_001281495.2	c.1123G>A	p.Glu375Lys	missense_variant	12/17
CTNNBL1	XM_024451947.2	c.1123G>A	p.Glu375Lys	missense_variant	12/17
CTNNBL1	XM_011528917.3	c.874G>A	p.Glu292Lys	missense_variant	9/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.1204G>A	p.Glu402Lys	missense_variant	11/16	1	NM_030877.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 08, 2023

The c.1204G>A (p.E402K) 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 1204, causing the glutamic acid (E) at amino acid position 402 to be replaced by a lysine (K). 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	0.64
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.52	.;.;D;.;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;.;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.68	D;D;D;D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.2	.;.;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.5	.;D;D;.;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	.;D;D;.;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;T
Polyphen		0.78, 0.84	.;.;P;.;P;.
Vest4		0.83
MutPred		0.40		.;.;Gain of methylation at E402 (P = 0.0088);.;.;.;
MVP		0.64
MPC		0.63
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.81
gMVP		0.76

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: chr20-36431441;