chr22-31837054-G-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.2253G>A(p.Ala751Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,890 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: not found (cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
DEPDC5
NM_001242896.3 synonymous
NM_001242896.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.301
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]
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=0.069).
BP6
Variant 22-31837054-G-A is Benign according to our data. Variant chr22-31837054-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 466466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.301 with no splicing effect.
BS2
High AC in GnomAdExome4 at 11 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001242896.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DEPDC5 | NM_001242896.3 | MANE Select | c.2253G>A | p.Ala751Ala | synonymous | Exon 26 of 43 | NP_001229825.1 | ||
| DEPDC5 | NM_001364318.2 | c.2253G>A | p.Ala751Ala | synonymous | Exon 26 of 43 | NP_001351247.1 | |||
| DEPDC5 | NM_001136029.4 | c.2226G>A | p.Ala742Ala | synonymous | Exon 26 of 43 | NP_001129501.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DEPDC5 | ENST00000651528.2 | MANE Select | c.2253G>A | p.Ala751Ala | synonymous | Exon 26 of 43 | ENSP00000498382.1 | ||
| DEPDC5 | ENST00000382112.8 | TSL:1 | c.2253G>A | p.Ala751Ala | synonymous | Exon 26 of 43 | ENSP00000371546.4 | ||
| DEPDC5 | ENST00000433147.2 | TSL:1 | c.2169G>A | p.Ala723Ala | synonymous | Exon 25 of 42 | ENSP00000410544.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000801 AC: 2AN: 249570 AF XY: 0.00000739 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
249570
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461890Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6AN XY: 727246 show subpopulations
GnomAD4 exome
AF:
AC:
11
AN:
1461890
Hom.:
Cov.:
34
AF XY:
AC XY:
6
AN XY:
727246
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33480
American (AMR)
AF:
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
2
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1112008
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.457
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
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
Nov 05, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
not provided Benign:1
Jun 01, 2020
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.