13-41076149-C-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_007187.5(WBP4):ā€‹c.668C>Gā€‹(p.Ser223*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā˜…). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

WBP4
NM_007187.5 stop_gained

Scores

3
3
1

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.44
Variant links:
Genes affected
WBP4 (HGNC:12739): (WW domain binding protein 4) This gene encodes WW domain-containing binding protein 4. The WW domain represents a small and compact globular structure that interacts with proline-rich ligands. This encoded protein is a general spliceosomal protein that may play a role in cross-intron bridging of U1 and U2 snRNPs in the spliceosomal complex A. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 13-41076149-C-G is Pathogenic according to our data. Variant chr13-41076149-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2500812.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WBP4NM_007187.5 linkc.668C>G p.Ser223* stop_gained Exon 8 of 10 ENST00000379487.5 NP_009118.1 O75554-1
WBP4XM_005266245.3 linkc.761C>G p.Ser254* stop_gained Exon 8 of 10 XP_005266302.1
WBP4XM_047430071.1 linkc.200C>G p.Ser67* stop_gained Exon 3 of 5 XP_047286027.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WBP4ENST00000379487.5 linkc.668C>G p.Ser223* stop_gained Exon 8 of 10 1 NM_007187.5 ENSP00000368801.3 O75554-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461816
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727208
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Neurodevelopmental disorder Pathogenic:1
May 01, 2023
Hadassah Hebrew University Medical Center
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.57
D
BayesDel_noAF
Pathogenic
0.59
CADD
Pathogenic
36
DANN
Uncertain
1.0
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.91
D
Vest4
0.21
GERP RS
3.4

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr13-41650285; API