rs587777458
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001242896.3(DEPDC5):c.3259C>G(p.Arg1087Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
DEPDC5
NM_001242896.3 missense
NM_001242896.3 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 2.42
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, DEPDC5
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2439478).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.3259C>G | p.Arg1087Gly | missense_variant | 32/43 | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.3259C>G | p.Arg1087Gly | missense_variant | 32/43 | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000417 AC: 1AN: 239714Hom.: 0 AF XY: 0.00000769 AC XY: 1AN XY: 129986
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1457770Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724686
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GnomAD4 genome ? Cov.: 32
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Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial focal epilepsy with variable foci Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 977884). This variant has not been reported in the literature in individuals affected with DEPDC5-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1087 of the DEPDC5 protein (p.Arg1087Gly). - |
Epilepsy, familial focal, with variable foci 1 Benign:1
Likely benign, no assertion criteria provided | clinical testing | Service de Génétique Moléculaire, Hôpital Robert Debré | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;.;.;D;D;.;D;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.;.;N;.;.;.;N;.;.;N;.
REVEL
Benign
Sift
Benign
T;.;.;.;.;.;T;.;.;.;D;.;.;D;.
Sift4G
Benign
T;.;.;.;.;.;T;.;.;.;D;.;.;D;.
Polyphen
1.0
.;.;D;.;.;.;.;.;.;.;.;.;D;.;.
Vest4
MVP
MPC
1.1
ClinPred
D
GERP RS
Varity_R
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at