dbSNP rs374648098: DEPDC1:p.Ser736Cys (chr1-68477878-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001114120.3(DEPDC1):c.2207C>G(p.Ser736Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000022 in 1,589,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

DEPDC1
NM_001114120.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.07

Publications

0 publications found

Variant links:

Genes affected

DEPDC1 (HGNC:22949): (DEP domain containing 1) Predicted to enable GTPase activator activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

DEPDC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16215158).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114120.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEPDC1	NM_001114120.3	MANE Select	c.2207C>G	p.Ser736Cys	missense	Exon 11 of 12	NP_001107592.1	Q5TB30-5
	DEPDC1	NM_017779.6		c.1355C>G	p.Ser452Cys	missense	Exon 10 of 11	NP_060249.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEPDC1	ENST00000456315.7	TSL:1 MANE Select	c.2207C>G	p.Ser736Cys	missense	Exon 11 of 12	ENSP00000412292.2	Q5TB30-5
DEPDC1	ENST00000370966.9	TSL:1	c.1355C>G	p.Ser452Cys	missense	Exon 10 of 11	ENSP00000360005.5	Q5TB30-2
DEPDC1	ENST00000489862.1	TSL:1	n.*424C>G		non_coding_transcript_exon	Exon 12 of 13	ENSP00000436464.1	H0YES2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151790

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000247

AC:

AN:

242794

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000314

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000345

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1437666

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

713824

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32942

American (AMR)

AF:

0.0000233

AC:

AN:

42928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25626

East Asian (EAS)

AF:

0.000153

AC:

AN:

39116

South Asian (SAS)

AF:

0.00

AC:

AN:

79652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1099444

Other (OTH)

AF:

0.000354

AC:

AN:

59352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000329

AC:

AN:

151790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41368

American (AMR)

AF:

0.0000657

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.000581

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67852

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

M_CAP

Benign

0.0082

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

PhyloP100

5.1

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.1

REVEL

Benign

0.079

Sift

Benign

0.061

Sift4G

Uncertain

0.043

Polyphen

0.29

Vest4

0.43

MutPred

0.30

Loss of disorder (P = 0.0146)

MVP

0.54

MPC

0.57

ClinPred

0.057

GERP RS

5.7

Varity_R

0.18

gMVP

0.31

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over