chr20-37779284-G-T

Variant names:

• chr20-37779284-G-T
• rs756755975
• NM_030877.5:c.980G>T

Variant summary

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

The NM_030877.5(CTNNBL1):​c.980G>T​(p.Arg327Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CTNNBL1 NM_030877.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.75

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, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.980G>T	p.Arg327Leu	missense_variant	Exon 10 of 16	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.899G>T	p.Arg300Leu	missense_variant	Exon 11 of 17		NP_001268424.1
CTNNBL1	XM_024451947.2	c.899G>T	p.Arg300Leu	missense_variant	Exon 11 of 17		XP_024307715.1
CTNNBL1	XM_011528917.3	c.650G>T	p.Arg217Leu	missense_variant	Exon 8 of 14		XP_011527219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.980G>T	p.Arg327Leu	missense_variant	Exon 10 of 16	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.899G>T	p.Arg300Leu	missense_variant	Exon 11 of 17	2		ENSP00000487198.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251354 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135838

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461516 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727066

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	.;.;D;.;.;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;.;D;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	2.9	.;.;M;.;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.9	.;D;D;.;D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0030	.;D;D;.;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;D
Polyphen		0.99, 1.0	.;.;D;.;D;.
Vest4		0.83
MutPred		0.39		.;.;Gain of helix (P = 0.0143);.;.;.;
MVP		0.63
MPC		1.4
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.90
gMVP		0.85

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: rs756755975; hg19: chr20-36407686;