12-14790467-C-A

Variant names:

• chr12-14790467-C-A
• NM_016312.3:c.1298G>T

Variant summary

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

The NM_016312.3(WBP11):​c.1298G>T​(p.Gly433Val) variant causes a missense change. 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: WBP11 NM_016312.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98

Genes affected

WBP11 (HGNC:16461): (WW domain binding protein 11) This gene encodes a nuclear protein, which colocalizes with mRNA splicing factors and intermediate filament-containing perinuclear networks. This protein has 95% amino acid sequence identity to the mouse Wbp11 protein. It contains two proline-rich regions that bind to the WW domain of Npw38, a nuclear protein, and thus this protein is also called Npw38-binding protein NpwBP. The Npw38-NpwBP complex may function as a component of an mRNA factory in the nucleus. [provided by RefSeq, Jul 2008]

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
WBP11	NM_016312.3	c.1298G>T	p.Gly433Val	missense_variant	Exon 10 of 12	ENST00000261167.7	NP_057396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP11	ENST00000261167.7	c.1298G>T	p.Gly433Val	missense_variant	Exon 10 of 12	1	NM_016312.3	ENSP00000261167.2
WBP11	ENST00000535638.5	n.*379G>T		downstream_gene_variant		5		ENSP00000443420.1

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 provided Uncertain:1

Feb 02, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.9	L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.67
MutPred		0.29		Loss of glycosylation at P432 (P = 0.0897);
MVP		0.17
MPC		0.73
ClinPred		0.82	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.28

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: chr12-14943401; COSMIC: COSV53762852; COSMIC: COSV53762852;