rs5998135

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3 link	c.1323A>C	p.Thr441Thr	splice_region_variant, synonymous_variant	Exon 19 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.1323A>C	p.Thr441Thr	splice_region_variant, synonymous_variant	Exon 19 of 43		NM_001242896.3	ENSP00000498382.1		O75140-10
ENSG00000285404	ENST00000646701.1 link	c.1239A>C	p.Thr413Thr	splice_region_variant, synonymous_variant	Exon 17 of 21			ENSP00000496158.1		A0A2R8YF50

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

GnomAD3 exomes

AF:

0.106

AC:

26358

AN:

249318

Hom.:

1651

AF XY:

0.101

AC XY:

13613

AN XY:

135274

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 SAS exome

AF:

0.0505

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

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0311

Gnomad4 SAS exome

AF:

0.0510

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.100

Gnomad4 OTH exome

AF:

0.0954

GnomAD4 genome

AF:

0.111

AC:

16832

AN:

152236

Hom.:

987

Cov.:

AF XY:

0.109

AC XY:

8138

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.0368

Gnomad4 SAS

AF:

0.0439

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.102

Hom.:

1409

Bravo

AF:

0.115

Asia WGS

AF:

0.0720

AC:

251

AN:

3478

EpiCase

AF:

0.0979

EpiControl

AF:

0.106

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 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

Jan 08, 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

-0.80

CADD

Benign

1.3

DANN

Benign

0.68

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

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