rs578244490
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_001242896.3(DEPDC5):c.3461C>T(p.Ser1154Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000878 in 1,583,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001242896.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.3461C>T | p.Ser1154Phe | missense_variant | 34/43 | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.3461C>T | p.Ser1154Phe | missense_variant | 34/43 | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000816 AC: 18AN: 220714Hom.: 0 AF XY: 0.0000416 AC XY: 5AN XY: 120152
GnomAD4 exome AF: 0.0000943 AC: 135AN: 1431504Hom.: 0 Cov.: 31 AF XY: 0.0000984 AC XY: 70AN XY: 711586
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 01, 2019 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
DEPDC5-related condition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 31, 2023 | The DEPDC5 c.3461C>T variant is predicted to result in the amino acid substitution p.Ser1154Phe. This variant was reported in an family with epilepsy, however the variant did not segregate with the disease completely (Ricos et al. 2016. PubMed ID: 26505888 Figure 2). Functional studies show that this variant does not significantly affect the protein function (Dawson et al. 2019. PubMed ID: 31639411). This variant is reported in 0.015% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-32266706-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Familial focal epilepsy with variable foci Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | This missense change has been observed in individual(s) with clinical features of DEPDC5-related conditions (PMID: 26505888). This variant is present in population databases (rs578244490, gnomAD 0.01%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1154 of the DEPDC5 protein (p.Ser1154Phe). ClinVar contains an entry for this variant (Variation ID: 264763). 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. Experimental studies have shown that this missense change does not substantially affect DEPDC5 function (PMID: 31639411). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. - |
Epilepsy, familial focal, with variable foci 1 Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at