NM_001242896.3:c.4809G>A
Variant names:
Variant summary
Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001242896.3(DEPDC5):c.4809G>A(p.Pro1603Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,588 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
DEPDC5
NM_001242896.3 synonymous
NM_001242896.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.91
Publications
0 publications found
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]
DEPDC5 Gene-Disease associations (from GenCC):
- epilepsy, familial focal, with variable foci 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P
- focal epilepsyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- autosomal dominant epilepsy with auditory featuresInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- autosomal dominant nocturnal frontal lobe epilepsyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial focal epilepsy with variable fociInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Brugada syndromeInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -15 ACMG points.
BP4
Computational evidence support a benign effect (REVEL=0.028).
BP6
Variant 22-31906494-G-A is Benign according to our data. Variant chr22-31906494-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 534816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.91 with no splicing effect.
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.4809G>A | p.Pro1603Pro | synonymous_variant | Exon 43 of 43 | NM_001242896.3 | ENSP00000498382.1 | |||
ENSG00000285404 | ENST00000646701.1 | c.1787-49645G>A | intron_variant | Intron 20 of 20 | ENSP00000496158.1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152268Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
10
AN:
152268
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
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Gnomad OTH
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GnomAD2 exomes AF: 0.0000564 AC: 14AN: 248316 AF XY: 0.0000666 show subpopulations
GnomAD2 exomes
AF:
AC:
14
AN:
248316
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461202Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 726848 show subpopulations
GnomAD4 exome
AF:
AC:
34
AN:
1461202
Hom.:
Cov.:
32
AF XY:
AC XY:
21
AN XY:
726848
show subpopulations
African (AFR)
AF:
AC:
5
AN:
33478
American (AMR)
AF:
AC:
7
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26130
East Asian (EAS)
AF:
AC:
10
AN:
39692
South Asian (SAS)
AF:
AC:
5
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
52940
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1111830
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
2
4
6
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10
0.00
0.20
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0.60
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome AF: 0.0000656 AC: 10AN: 152386Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74518 show subpopulations
GnomAD4 genome
AF:
AC:
10
AN:
152386
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74518
show subpopulations
African (AFR)
AF:
AC:
5
AN:
41592
American (AMR)
AF:
AC:
2
AN:
15312
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
2
AN:
5186
South Asian (SAS)
AF:
AC:
1
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10632
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68040
Other (OTH)
AF:
AC:
0
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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10
<30
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
4
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial focal epilepsy with variable foci Benign:1
Oct 22, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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