rs764462476
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4BP6
The NM_001242896.3(DEPDC5):c.4183G>A(p.Ala1395Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000404 in 1,607,870 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1395S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001242896.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.4183G>A | p.Ala1395Thr | missense_variant | 39/43 | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.4183G>A | p.Ala1395Thr | missense_variant | 39/43 | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152152Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000699 AC: 17AN: 243152Hom.: 0 AF XY: 0.0000606 AC XY: 8AN XY: 131998
GnomAD4 exome AF: 0.0000398 AC: 58AN: 1455718Hom.: 0 Cov.: 30 AF XY: 0.0000414 AC XY: 30AN XY: 724232
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152152Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74326
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 06, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2020 | - - |
Familial focal epilepsy with variable foci Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1395 of the DEPDC5 protein (p.Ala1395Thr). This variant is present in population databases (rs764462476, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DEPDC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 565734). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at