chr13-41065289-TAAAAAAAAA-T

Variant names:

• chr13-41065289-TAAAAAAAAA-T
• rs58699334
• NM_007187.5:c.262+15_262+23delAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000379487.5(WBP4):​c.262+3_262+11delAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000592 in 1,182,158 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: WBP4 ENST00000379487.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• 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 2 ACMG points.

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

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+15_262+23delAAAAAAAAA		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+3_262+11delAAAAAAAAA		splice_region intron	N/A	ENSP00000368801.3	O75554-1
	WBP4	ENST00000953016.1		c.262+3_262+11delAAAAAAAAA		splice_region intron	N/A	ENSP00000623075.1
	WBP4	ENST00000953017.1		c.199+3_199+11delAAAAAAAAA		splice_region intron	N/A	ENSP00000623076.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000592 AC: 7 AN: 1182158 Hom.: 0 AF XY: 0.00000694 AC XY: 4 AN XY: 576644

⚠️ 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: 0.0000619 AC: 1 AN: 16144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16968

East Asian (EAS) AF: 0.00 AC: 0 AN: 30138

South Asian (SAS) AF: 0.0000188 AC: 1 AN: 53152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25192

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

European-Non Finnish (NFE) AF: 0.00000415 AC: 4 AN: 963978

Other (OTH) AF: 0.0000209 AC: 1 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		0.97

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs58699334;

hg19: chr13-41639425;