chr4-84672953-ATTTTC-TTTTT
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP2
The NM_014991.6(WDFY3):c.10491_10496delGAAAATinsAAAAA(p.Ile3499fs) variant causes a frameshift, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
WDFY3
NM_014991.6 frameshift, missense
NM_014991.6 frameshift, missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.54
Genes affected
WDFY3 (HGNC:20751): (WD repeat and FYVE domain containing 3) This gene encodes a phosphatidylinositol 3-phosphate-binding protein that functions as a master conductor for aggregate clearance by autophagy. This protein shuttles from the nuclear membrane to colocalize with aggregated proteins, where it complexes with other autophagic components to achieve macroautophagy-mediated clearance of these aggregated proteins. However, it is not necessary for starvation-induced macroautophagy. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00851 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), WDFY3. . Gene score misZ 5.8174 (greater than the threshold 3.09). Trascript score misZ 7.6797 (greater than threshold 3.09). GenCC has associacion of gene with syndromic intellectual disability, complex neurodevelopmental disorder, autism spectrum disorder.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WDFY3 | NM_014991.6 | c.10491_10496delGAAAATinsAAAAA | p.Ile3499fs | frameshift_variant, missense_variant | 68/68 | ENST00000295888.9 | NP_055806.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WDFY3 | ENST00000295888.9 | c.10491_10496delGAAAATinsAAAAA | p.Ile3499fs | frameshift_variant, missense_variant | 68/68 | 1 | NM_014991.6 | ENSP00000295888.4 | ||
WDFY3 | ENST00000425179.2 | n.1243_1248delGAAAATinsAAAAA | non_coding_transcript_exon_variant | 5/5 | 1 | |||||
WDFY3 | ENST00000514711.2 | c.8931_8936delGAAAATinsAAAAA | p.Ile2979fs | frameshift_variant, missense_variant | 57/57 | 2 | ENSP00000424987.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant in which the last 28 amino acids are replaced with 33 different amino acids; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.