Genetic Variant DEPDC1:p.Gly5Cys (chr1-68496987-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001114120.3(DEPDC1):c.13G>T(p.Gly5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

DEPDC1
NM_001114120.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.217

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:

DEPDC1-AS1 (HGNC:50592): (DEPDC1 antisense RNA 1)

DEPDC1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053535968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC1	NM_001114120.3 link	c.13G>T	p.Gly5Cys	missense_variant	Exon 1 of 12	ENST00000456315.7	NP_001107592.1	Q5TB30-5
DEPDC1	NM_017779.6 link	c.13G>T	p.Gly5Cys	missense_variant	Exon 1 of 11		NP_060249.2	Q5TB30-2
DEPDC1-AS1	NR_110671.1 link	n.96+216C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DEPDC1	ENST00000456315.7 link	c.13G>T	p.Gly5Cys	missense_variant	Exon 1 of 12	1	NM_001114120.3	ENSP00000412292.2	Q5TB30-5
DEPDC1	ENST00000370966.9 link	c.13G>T	p.Gly5Cys	missense_variant	Exon 1 of 11	1		ENSP00000360005.5	Q5TB30-2
DEPDC1-AS1	ENST00000428732.1 link	n.96+216C>A		intron_variant	Intron 1 of 2	1
DEPDC1	ENST00000525124.1 link	c.-385G>T		5_prime_UTR_variant	Exon 1 of 5	3		ENSP00000431477.1	E9PL61

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249088

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134740

show subpopulations

Gnomad AFR exome

AF:

0.000434

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461124

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000112

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.13G>T (p.G5C) alteration is located in exon 1 (coding exon 1) of the DEPDC1 gene. This alteration results from a G to T substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0043

T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.026

Sift

Benign

0.073

T;T

Sift4G

Benign

0.088

T;T

Polyphen

0.88

P;P

Vest4

0.19

MutPred

0.23

Loss of disorder (P = 0.0532);Loss of disorder (P = 0.0532);

MVP

0.28

MPC

0.36

ClinPred

0.16

GERP RS

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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