rs886039276

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_001242896.3(DEPDC5):ā€‹c.640C>Gā€‹(p.His214Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,458,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.0000082 ( 0 hom. )

Consequence

DEPDC5
NM_001242896.3 missense

Scores

13
5
1

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 7.16
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DEPDC5. . Gene score misZ 2.6501 (greater than the threshold 3.09). Trascript score misZ 3.7275 (greater than threshold 3.09). GenCC has associacion of gene with focal epilepsy, Brugada syndrome, epilepsy, familial focal, with variable foci 1, familial focal epilepsy with variable foci, autosomal dominant epilepsy with auditory features, autosomal dominant nocturnal frontal lobe epilepsy.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DEPDC5NM_001242896.3 linkuse as main transcriptc.640C>G p.His214Asp missense_variant 11/43 ENST00000651528.2 NP_001229825.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DEPDC5ENST00000651528.2 linkuse as main transcriptc.640C>G p.His214Asp missense_variant 11/43 NM_001242896.3 ENSP00000498382 P4O75140-10

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000823
AC:
12
AN:
1458704
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
725752
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

Epilepsy, familial focal, with variable foci 1 Other:1
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.80
.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;D;.;.;.;.;.;.
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D;D;D;D;D;.;.;D;D;.;.;D;D;.;D;D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Pathogenic
0.85
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.41
D
MutationAssessor
Pathogenic
3.2
M;.;.;M;M;.;.;M;M;.;M;.;M;.;M;M;.;.;M;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Pathogenic
-7.9
D;.;.;.;.;.;.;.;D;.;D;.;.;.;D;D;.;.;D;D;.;.
REVEL
Pathogenic
0.65
Sift
Pathogenic
0.0
D;.;.;.;.;.;.;.;D;.;D;.;.;.;D;D;.;.;D;D;.;.
Sift4G
Uncertain
0.0090
D;.;.;.;.;.;.;.;D;.;D;.;.;.;D;D;.;.;D;D;.;.
Polyphen
1.0, 0.99
.;.;.;.;.;.;.;D;D;.;.;.;.;.;D;D;.;.;.;.;.;.
Vest4
0.95
MutPred
0.69
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;
MVP
0.73
MPC
1.4
ClinPred
1.0
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs886039276; hg19: chr22-32188034; COSMIC: COSV56691849; COSMIC: COSV56691849; API