rs587776975

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001242896.3(DEPDC5):​c.4107G>A​(p.Trp1369Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,746 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DEPDC5
NM_001242896.3 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:2O:1

Conservation

PhyloP100: 9.64
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 Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 22-31893655-G-A is Pathogenic according to our data. Variant chr22-31893655-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 50822.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DEPDC5NM_001242896.3 linkuse as main transcriptc.4107G>A p.Trp1369Ter stop_gained 39/43 ENST00000651528.2 NP_001229825.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DEPDC5ENST00000651528.2 linkuse as main transcriptc.4107G>A p.Trp1369Ter stop_gained 39/43 NM_001242896.3 ENSP00000498382 P4O75140-10

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461746
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727178
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Epilepsy, familial focal, with variable foci 1 Pathogenic:1Other:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMay 09, 2014- -
not provided, no classification providedliterature onlyGeneReviews-- -
Autosomal dominant epilepsy Pathogenic:1
Pathogenic, no assertion criteria providedresearchRare Disease Center, Seoul National University HospitalMar 23, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.65
CADD
Pathogenic
43
DANN
Uncertain
1.0
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
A;A;A;A;A;A;A;A;D
Vest4
0.77
ClinPred
0.99
D
GERP RS
5.0

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: rs587776975; hg19: chr22-32289641; API