13-41072793-GA-G

Variant names:

• chr13-41072793-GA-G
• NM_007187.5:c.499delA

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_007187.5(WBP4):​c.499delA​(p.Thr167ProfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WBP4 NM_007187.5 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1 O:1
• Conservation: PhyloP100: -0.150

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]

ACMG classification

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 13-41072793-GA-G is Pathogenic according to our data. Variant chr13-41072793-GA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2500810.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WBP4	NM_007187.5	c.499delA	p.Thr167ProfsTer4	frameshift_variant	Exon 7 of 10	ENST00000379487.5	NP_009118.1
WBP4	XM_005266245.3	c.592delA	p.Thr198ProfsTer4	frameshift_variant	Exon 7 of 10		XP_005266302.1
WBP4	XM_047430071.1	c.31delA	p.Thr11ProfsTer4	frameshift_variant	Exon 2 of 5		XP_047286027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP4	ENST00000379487.5	c.499delA	p.Thr167ProfsTer4	frameshift_variant	Exon 7 of 10	1	NM_007187.5	ENSP00000368801.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: criteria provided, single submitter

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

- -

Neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities Other:1

Jun 18, 2024

OMIM

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

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: chr13-41646929;