rs79070552

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001242896.3(DEPDC5):c.1095T>C(p.Asp365Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,613,836 control chromosomes in the GnomAD database, including 375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 60 hom., cov: 32)

Exomes 𝑓: 0.020 ( 315 hom. )

Consequence

DEPDC5
NM_001242896.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.290

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]

DEPDC5 links:

ENSG00000285404 (HGNC:):

ENSG00000285404 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 22-31804175-T-C is Benign according to our data. Variant chr22-31804175-T-C is described in ClinVar as [Benign]. Clinvar id is 257657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31804175-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0251 (3817/152176) while in subpopulation AFR AF= 0.0413 (1716/41520). AF 95% confidence interval is 0.0397. There are 60 homozygotes in gnomad4. There are 1887 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3 link	c.1095T>C	p.Asp365Asp	synonymous_variant	Exon 16 of 43	ENST00000651528.2	NP_001229825.1	O75140-10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2 link	c.1095T>C	p.Asp365Asp	synonymous_variant	Exon 16 of 43		NM_001242896.3	ENSP00000498382.1		O75140-10
ENSG00000285404	ENST00000646701.1 link	c.1011T>C	p.Asp337Asp	synonymous_variant	Exon 14 of 21			ENSP00000496158.1		A0A2R8YF50

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3812

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00386

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0246

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0201

AC:

5021

AN:

249492

Hom.:

AF XY:

0.0201

AC XY:

2722

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.0413

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.00993

Gnomad EAS exome

AF:

0.00406

Gnomad SAS exome

AF:

0.0232

Gnomad FIN exome

AF:

0.0242

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0239

GnomAD4 exome

AF:

0.0197

AC:

28817

AN:

1461660

Hom.:

315

Cov.:

AF XY:

0.0199

AC XY:

14439

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0423

Gnomad4 AMR exome

AF:

0.0172

Gnomad4 ASJ exome

AF:

0.00815

Gnomad4 EAS exome

AF:

0.00280

Gnomad4 SAS exome

AF:

0.0232

Gnomad4 FIN exome

AF:

0.0248

Gnomad4 NFE exome

AF:

0.0195

Gnomad4 OTH exome

AF:

0.0201

GnomAD4 genome

AF:

0.0251

AC:

3817

AN:

152176

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1887

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0413

Gnomad4 AMR

AF:

0.0200

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00386

Gnomad4 SAS

AF:

0.0216

Gnomad4 FIN

AF:

0.0246

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0217

Hom.:

Bravo

AF:

0.0263

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0212

EpiControl

AF:

0.0215

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 02, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Familial focal epilepsy with variable foci

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.8

DANN

Benign

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over