13-41065289-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr13-41065289-T-TAAAAAAAAAAAAA
• rs58699334
• NM_007187.5:c.262+11_262+23dupAAAAAAAAAAAAA

Variant summary

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

The ENST00000379487.5(WBP4):​c.262+2_262+3insAAAAAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000012 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WBP4 ENST00000379487.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 1 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+11_262+23dupAAAAAAAAAAAAA		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+3insAAAAAAAAAAAAA		splice_region intron	N/A	ENSP00000368801.3	O75554-1
	WBP4	ENST00000953016.1		c.262+2_262+3insAAAAAAAAAAAAA		splice_region intron	N/A	ENSP00000623075.1
	WBP4	ENST00000953017.1		c.199+2_199+3insAAAAAAAAAAAAA		splice_region intron	N/A	ENSP00000623076.1

Frequencies

GnomAD3 genomes AF: 0.0000122 AC: 1 AN: 81792 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000244

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000254 AC: 3 AN: 1182182 Hom.: 0 Cov.: 0 AF XY: 0.00000520 AC XY: 3 AN XY: 576660

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

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

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

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

South Asian (SAS) AF: 0.0000188 AC: 1 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: 0.00000104 AC: 1 AN: 963992

Other (OTH) AF: 0.0000209 AC: 1 AN: 47860

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000122 AC: 1 AN: 81792 Hom.: 0 Cov.: 25 AF XY: 0.0000262 AC XY: 1 AN XY: 38222

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

African (AFR) AF: 0.00 AC: 0 AN: 21186

American (AMR) AF: 0.00 AC: 0 AN: 7074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2088

East Asian (EAS) AF: 0.00 AC: 0 AN: 2828

South Asian (SAS) AF: 0.00 AC: 0 AN: 2628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 112

European-Non Finnish (NFE) AF: 0.0000244 AC: 1 AN: 41004

Other (OTH) AF: 0.00 AC: 0 AN: 1088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

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;