13-41065289-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr13-41065289-T-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
• rs58699334
• NM_007187.5:c.262+23_262+24insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000379487.5(WBP4):​c.262+2_262+3insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,182,182 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: WBP4 ENST00000379487.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 0 publications found

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]

WBP4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379487.5. 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
	WBP4	NM_007187.5	MANE Select	c.262+23_262+24insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		intron	N/A	NP_009118.1	O75554-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WBP4	ENST00000379487.5	TSL:1 MANE Select	c.262+2_262+3insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		splice_region intron	N/A	ENSP00000368801.3	O75554-1
	WBP4	ENST00000953016.1		c.262+2_262+3insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		splice_region intron	N/A	ENSP00000623075.1
	WBP4	ENST00000953017.1		c.199+2_199+3insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA		splice_region intron	N/A	ENSP00000623076.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 8.46e-7 AC: 1 AN: 1182182 Hom.: 0 Cov.: 0 AF XY: 0.00000173 AC XY: 1 AN XY: 576660

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25344

American (AMR) AF: 0.00 AC: 0 AN: 16146

Ashkenazi Jewish (ASJ) AF: 0.0000589 AC: 1 AN: 16968

East Asian (EAS) AF: 0.00 AC: 0 AN: 30142

South Asian (SAS) AF: 0.00 AC: 0 AN: 53154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3382

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 963992

Other (OTH) AF: 0.00 AC: 0 AN: 47860

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.085

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58699334; hg19: chr13-41639425;