rs5998135

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001242896.3(DEPDC5):c.1323A>C(p.Thr441Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,613,484 control chromosomes in the GnomAD database, including 8,690 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 987 hom., cov: 32)

Exomes 𝑓: 0.099 ( 7703 hom. )

Consequence

DEPDC5
NM_001242896.3 splice_region, synonymous

Scores

Splicing: ADA: 0.01390

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.926

Publications

9 publications found

Variant links:

COSMIC-nc: COSV56697481

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 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P
focal epilepsy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant epilepsy with auditory features
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal dominant nocturnal frontal lobe epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial focal epilepsy with variable foci
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Brugada syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DEPDC5 links:

ENSG00000285404 (HGNC:):

ENSG00000285404 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 22-31809646-A-C is Benign according to our data. Variant chr22-31809646-A-C is described in ClinVar as Benign. ClinVar VariationId is 257658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DEPDC5	NM_001242896.3	MANE Select	c.1323A>C	p.Thr441Thr	splice_region synonymous	Exon 19 of 43	NP_001229825.1
DEPDC5	NM_001364318.2		c.1323A>C	p.Thr441Thr	splice_region synonymous	Exon 19 of 43	NP_001351247.1
DEPDC5	NM_001136029.4		c.1323A>C	p.Thr441Thr	splice_region synonymous	Exon 19 of 43	NP_001129501.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DEPDC5	ENST00000651528.2	MANE Select	c.1323A>C	p.Thr441Thr	splice_region synonymous	Exon 19 of 43	ENSP00000498382.1
DEPDC5	ENST00000382112.8	TSL:1	c.1323A>C	p.Thr441Thr	splice_region synonymous	Exon 19 of 43	ENSP00000371546.4
DEPDC5	ENST00000433147.2	TSL:1	c.1239A>C	p.Thr413Thr	splice_region synonymous	Exon 18 of 42	ENSP00000410544.2

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16803

AN:

152118

Hom.:

984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0367

Gnomad SAS

AF:

0.0443

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.109

GnomAD2 exomes

AF:

0.106

AC:

26358

AN:

249318

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.187

Gnomad ASJ exome

AF:

0.0993

Gnomad EAS exome

AF:

0.0392

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0991

AC:

144829

AN:

1461248

Hom.:

7703

Cov.:

AF XY:

0.0971

AC XY:

70603

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.121

AC:

4061

AN:

33472

American (AMR)

AF:

0.181

AC:

8113

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2688

AN:

26128

East Asian (EAS)

AF:

0.0311

AC:

1236

AN:

39694

South Asian (SAS)

AF:

0.0510

AC:

4403

AN:

86250

European-Finnish (FIN)

AF:

0.127

AC:

6753

AN:

53348

Middle Eastern (MID)

AF:

0.0889

AC:

513

AN:

5768

European-Non Finnish (NFE)

AF:

0.100

AC:

111305

AN:

1111512

Other (OTH)

AF:

0.0954

AC:

5757

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

6204

12407

18611

24814

31018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4128

8256

12384

16512

20640

<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

AF:

0.111

AC:

16832

AN:

152236

Hom.:

987

Cov.:

AF XY:

0.109

AC XY:

8138

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.122

AC:

5079

AN:

41536

American (AMR)

AF:

0.149

AC:

2275

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

354

AN:

3472

East Asian (EAS)

AF:

0.0368

AC:

191

AN:

5190

South Asian (SAS)

AF:

0.0439

AC:

212

AN:

4824

European-Finnish (FIN)

AF:

0.125

AC:

1331

AN:

10608

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6963

AN:

68018

Other (OTH)

AF:

0.108

AC:

229

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

769

1538

2308

3077

3846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.102

Hom.:

3078

Bravo

AF:

0.115

Asia WGS

AF:

0.0720

AC:

251

AN:

3478

EpiCase

AF:

0.0979

EpiControl

AF:

0.106

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Familial focal epilepsy with variable foci (1)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

(source)

DANN

Benign

0.68

PhyloP100

-0.93

Mutation Taster

=68/32

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.014

dbscSNV1_RF

Benign

0.36

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over