12-14790552-G-A

Position:

• chr12-14790552-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_016312.3(WBP11):​c.1213C>T​(p.Pro405Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,614,008 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (23 hom.)
• Consequence: WBP11 NM_016312.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.51

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]

C12orf60 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), WBP11. . Gene score misZ 2.9803 (greater than the threshold 3.09). Trascript score misZ 3.4119 (greater than threshold 3.09). GenCC has associacion of gene with vertebral, cardiac, tracheoesophageal, renal, and limb defects.
• BP4: Computational evidence support a benign effect (MetaRNN=0.008779317).
• BP6: Variant 12-14790552-G-A is Benign according to our data. Variant chr12-14790552-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 489 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WBP11	NM_016312.3	c.1213C>T	p.Pro405Ser	missense_variant	10/12	ENST00000261167.7	NP_057396.1
C12orf60	XM_047428389.1	c.-517+4345G>A		intron_variant			XP_047284345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WBP11	ENST00000261167.7	c.1213C>T	p.Pro405Ser	missense_variant	10/12	1	NM_016312.3	ENSP00000261167	P1

Frequencies

GnomAD3 genomes AF: 0.00321 AC: 489 AN: 152224 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000892

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00573

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00346 AC: 868 AN: 251174 Hom.: 4 AF XY: 0.00360 AC XY: 489 AN XY: 135744

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00140

Gnomad FIN exome AF: 0.00226

Gnomad NFE exome AF: 0.00621

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00445 AC: 6503 AN: 1461668 Hom.: 23 Cov.: 31 AF XY: 0.00435 AC XY: 3163 AN XY: 727144

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000997

Gnomad4 FIN exome AF: 0.00234

Gnomad4 NFE exome AF: 0.00543

Gnomad4 OTH exome AF: 0.00301

GnomAD4 genome AF: 0.00321 AC: 489 AN: 152340 Hom.: 1 Cov.: 32 AF XY: 0.00315 AC XY: 235 AN XY: 74496

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00573

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00427 Hom.: 0

Bravo AF: 0.00293

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00535 AC: 46

ExAC AF: 0.00382 AC: 464

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00589

EpiControl AF: 0.00516

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

WBP11: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.43	T
Polyphen		0.98	D
Vest4		0.59
MVP		0.14
MPC		0.59
ClinPred		0.044	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.29

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: rs149086245; hg19: chr12-14943486; COSMIC: COSV53763530; COSMIC: COSV53763530;