NM_001242896.3:c.633C>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001242896.3(DEPDC5):c.633C>A(p.Asn211Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N211N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DEPDC5
NM_001242896.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.495

Publications

0 publications found

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 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25307077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3 link	c.633C>A	p.Asn211Lys	missense_variant	Exon 11 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.633C>A	p.Asn211Lys	missense_variant	Exon 11 of 43		NM_001242896.3	ENSP00000498382.1		O75140-10
ENSG00000285404	ENST00000646701.1 link	c.549C>A	p.Asn183Lys	missense_variant	Exon 9 of 21			ENSP00000496158.1		A0A2R8YF50

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453470

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33258

American (AMR)

AF:

0.00

AC:

AN:

44488

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25816

East Asian (EAS)

AF:

0.00

AC:

AN:

39214

South Asian (SAS)

AF:

0.00

AC:

AN:

86136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1106298

Other (OTH)

AF:

0.00

AC:

AN:

59880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

.;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D;D;D;D;.;.;D;D;.;.;D;D;.;D;D;D

M_CAP

Benign

0.063

MetaRNN

Benign

0.25

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.62

N;.;.;N;N;.;.;N;N;.;N;.;N;.;N;N;.;.;N;N;.;.

PhyloP100

0.49

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.9

D;.;.;.;.;.;.;.;D;.;D;.;.;.;D;D;.;.;D;D;.;.

REVEL

Benign

0.12

Sift

Uncertain

0.010

D;.;.;.;.;.;.;.;T;.;D;.;.;.;T;T;.;.;D;T;.;.

Sift4G

Benign

0.19

T;.;.;.;.;.;.;.;D;.;D;.;.;.;T;D;.;.;D;T;.;.

Polyphen

0.18, 1.0

.;.;.;.;.;.;.;B;D;.;.;.;.;.;B;D;.;.;.;.;.;.

Vest4

0.55

MutPred

0.43

Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);.;Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);.;Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);.;Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);.;

MVP

0.27

MPC

1.3

ClinPred

0.98

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

Mutation Taster

=32/68

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001242896.3:c.633C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over