rs587776974
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM4_SupportingPP5_Moderate
The NM_001242896.3(DEPDC5):c.489_491del(p.Phe164del) variant causes a inframe deletion change. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. V163V) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Consequence
DEPDC5
NM_001242896.3 inframe_deletion
NM_001242896.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.99
Genes affected
DEPDC5 (HGNC:18423): (DEP domain containing 5, GATOR1 subcomplex subunit) This gene encodes a member of the IML1 family of proteins involved in G-protein signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth by sensing the availability of nutrients. The protein encoded by this gene is a component of the GATOR1 (GAP activity toward Rags) complex which inhibits the amino acid-sensing branch of the mTORC1 pathway. Mutations in this gene are associated with autosomal dominant familial focal epilepsy with variable foci. A single nucleotide polymorphism in an intron of this gene has been associated with an increased risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001242896.3. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 22-31783910-GTGT-G is Pathogenic according to our data. Variant chr22-31783910-GTGT-G is described in ClinVar as [Pathogenic]. Clinvar id is 50821.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.489_491del | p.Phe164del | inframe_deletion | 9/43 | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.489_491del | p.Phe164del | inframe_deletion | 9/43 | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epilepsy, familial focal, with variable foci 1 Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2013 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 28, 2022 | In-frame deletion of 1 amino acid in a non-repeat region; Published functional studies demonstrate a damaging effect, as the variant deregulates mTORC1 inhibition in embryonic mouse neurons (Dawson et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27683934, 25366275, 10577924, 24283814, 26505888, 15329069, 31639411, 30093711, 34295225, 23542697) - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at