chr12-14790467-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

GUCY2C-AS1 (HGNC:56054): (GUCY2C antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016312.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WBP11	NM_016312.3	MANE Select	c.1298G>T	p.Gly433Val	missense	Exon 10 of 12	NP_057396.1	Q9Y2W2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WBP11	ENST00000261167.7	TSL:1 MANE Select	c.1298G>T	p.Gly433Val	missense	Exon 10 of 12	ENSP00000261167.2	Q9Y2W2
	WBP11	ENST00000858075.1		c.1298G>T	p.Gly433Val	missense	Exon 11 of 13	ENSP00000528134.1
	WBP11	ENST00000918140.1		c.1298G>T	p.Gly433Val	missense	Exon 10 of 12	ENSP00000588199.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.0
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
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

hg19: chr12-14943401; COSMIC: COSV53762852; COSMIC: COSV53762852;