chr20-37777412-A-C

Variant names:

• chr20-37777412-A-C
• rs137951659
• NM_030877.5:c.818A>C

Variant summary

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

The NM_030877.5(CTNNBL1):​c.818A>C​(p.Asn273Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNBL1 NM_030877.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.51

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=0.26705277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.818A>C	p.Asn273Thr	missense_variant	Exon 8 of 16	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.737A>C	p.Asn246Thr	missense_variant	Exon 9 of 17		NP_001268424.1
CTNNBL1	XM_024451947.2	c.737A>C	p.Asn246Thr	missense_variant	Exon 9 of 17		XP_024307715.1
CTNNBL1	XM_011528917.3	c.488A>C	p.Asn163Thr	missense_variant	Exon 6 of 14		XP_011527219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.818A>C	p.Asn273Thr	missense_variant	Exon 8 of 16	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.737A>C	p.Asn246Thr	missense_variant	Exon 9 of 17	2		ENSP00000487198.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251304 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.15	.;.;T;.;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.018
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D;D;.;D;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.27	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	.;.;N;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.15	.;N;N;.;N;N
REVEL	Benign	0.14
Sift	Benign	0.49	.;T;T;.;T;T
Sift4G	Benign	0.70	T;T;T;T;T;T
Polyphen		0.0	.;.;B;.;B;.
Vest4		0.65
MutPred		0.36		.;.;Loss of stability (P = 0.028);.;.;.;
MVP		0.52
MPC		0.45
ClinPred		0.33	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.18
gMVP		0.57

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: rs137951659; hg19: chr20-36405814;