4-84672953-ATTTTC-TTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_014991.6(WDFY3):​c.10491_10496delinsAAAAA​(p.Ile3499ThrfsTer34) variant causes a frameshift 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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.54
Variant links:
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 3563 codons.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WDFY3NM_014991.6 linkuse as main transcriptc.10491_10496delinsAAAAA p.Ile3499ThrfsTer34 frameshift_variant 68/68 ENST00000295888.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WDFY3ENST00000295888.9 linkuse as main transcriptc.10491_10496delinsAAAAA p.Ile3499ThrfsTer34 frameshift_variant 68/681 NM_014991.6 P1Q8IZQ1-1
WDFY3ENST00000425179.2 linkuse as main transcriptn.1243_1248delinsAAAAA non_coding_transcript_exon_variant 5/51
WDFY3ENST00000514711.2 linkuse as main transcriptc.8931_8936delinsAAAAA p.Ile2979ThrfsTer34 frameshift_variant 57/572

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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 submitterclinical testingGeneDxMar 18, 2023Not 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: chr4-85594106; API