rs16989495

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001242896.3(DEPDC5):c.885A>G(p.Gln295Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,610,742 control chromosomes in the GnomAD database, including 1,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 109 hom., cov: 31)

Exomes 𝑓: 0.035 ( 1015 hom. )

Consequence

DEPDC5
NM_001242896.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0840

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=-0.71).

BP6

Variant 22-31798595-A-G is Benign according to our data. Variant chr22-31798595-A-G is described in ClinVar as [Benign]. Clinvar id is 257663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31798595-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.084 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3 link	c.885A>G	p.Gln295Gln	synonymous_variant	Exon 14 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.885A>G	p.Gln295Gln	synonymous_variant	Exon 14 of 43		NM_001242896.3	ENSP00000498382.1		O75140-10
ENSG00000285404	ENST00000646701.1 link	c.801A>G	p.Gln267Gln	synonymous_variant	Exon 12 of 21			ENSP00000496158.1		A0A2R8YF50

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5127

AN:

152160

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0241

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.0633

Gnomad FIN

AF:

0.0834

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0358

AC:

8907

AN:

249028

Hom.:

225

AF XY:

0.0378

AC XY:

5104

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.0269

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.0203

Gnomad SAS exome

AF:

0.0535

Gnomad FIN exome

AF:

0.0768

Gnomad NFE exome

AF:

0.0343

Gnomad OTH exome

AF:

0.0318

GnomAD4 exome

AF:

0.0346

AC:

50446

AN:

1458464

Hom.:

1015

Cov.:

AF XY:

0.0353

AC XY:

25607

AN XY:

725628

show subpopulations

Gnomad4 AFR exome

AF:

0.0256

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.0254

Gnomad4 EAS exome

AF:

0.0263

Gnomad4 SAS exome

AF:

0.0560

Gnomad4 FIN exome

AF:

0.0722

Gnomad4 NFE exome

AF:

0.0327

Gnomad4 OTH exome

AF:

0.0343

GnomAD4 genome

AF:

0.0337

AC:

5126

AN:

152278

Hom.:

109

Cov.:

AF XY:

0.0368

AC XY:

2743

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0241

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.0226

Gnomad4 SAS

AF:

0.0634

Gnomad4 FIN

AF:

0.0834

Gnomad4 NFE

AF:

0.0342

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0320

Hom.:

122

Bravo

AF:

0.0275

Asia WGS

AF:

0.0340

AC:

120

AN:

3478

EpiCase

AF:

0.0358

EpiControl

AF:

0.0322

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 26, 2018

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

- -

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 02, 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

-0.71

CADD

Benign

6.3

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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