NM_030877.5:c.1351G>T

Variant names:

• chr20-37842378-G-T
• rs144638509
• NM_030877.5:c.1351G>T

Variant summary

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

The NM_030877.5(CTNNBL1):​c.1351G>T​(p.Ala451Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,176 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.98

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 rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.1351G>T	p.Ala451Ser	missense_variant	Exon 13 of 16	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.1270G>T	p.Ala424Ser	missense_variant	Exon 14 of 17		NP_001268424.1
CTNNBL1	XM_024451947.2	c.1270G>T	p.Ala424Ser	missense_variant	Exon 14 of 17		XP_024307715.1
CTNNBL1	XM_011528917.3	c.1021G>T	p.Ala341Ser	missense_variant	Exon 11 of 14		XP_011527219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.1351G>T	p.Ala451Ser	missense_variant	Exon 13 of 16	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.1270G>T	p.Ala424Ser	missense_variant	Exon 14 of 17	2		ENSP00000487198.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;.;T;.;.;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D;.;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.62	D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;.;L;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.28	.;N;N;.;N;N
REVEL	Benign	0.19
Sift	Benign	0.069	.;T;D;.;D;T
Sift4G	Benign	0.062	T;T;T;T;T;T
Polyphen		0.15, 0.33	.;.;B;.;B;.
Vest4		0.69
MutPred		0.46		.;.;Loss of helix (P = 0.028);.;.;.;
MVP		0.45
MPC		0.44
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.35
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs144638509; hg19: chr20-36470780;