1-68496987-C-A

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

1
18

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

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
DEPDC1NM_001114120.3 linkc.13G>T p.Gly5Cys missense_variant Exon 1 of 12 ENST00000456315.7 NP_001107592.1 Q5TB30-5
DEPDC1NM_017779.6 linkc.13G>T p.Gly5Cys missense_variant Exon 1 of 11 NP_060249.2 Q5TB30-2
DEPDC1-AS1NR_110671.1 linkn.96+216C>A intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DEPDC1ENST00000456315.7 linkc.13G>T p.Gly5Cys missense_variant Exon 1 of 12 1 NM_001114120.3 ENSP00000412292.2 Q5TB30-5
DEPDC1ENST00000370966.9 linkc.13G>T p.Gly5Cys missense_variant Exon 1 of 11 1 ENSP00000360005.5 Q5TB30-2
DEPDC1-AS1ENST00000428732.1 linkn.96+216C>A intron_variant Intron 1 of 2 1
DEPDC1ENST00000525124.1 linkc.-385G>T 5_prime_UTR_variant Exon 1 of 5 3 ENSP00000431477.1 E9PL61

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152220
Hom.:
0
Cov.:
32
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:
7
AN:
249088
Hom.:
0
AF XY:
0.00000742
AC XY:
1
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:
10
AN:
1461124
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
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:
17
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
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.:
0
Bravo
AF:
0.000113
ExAC
AF:
0.0000330
AC:
4

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
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0043
T;.
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.060
D
MetaRNN
Benign
0.054
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Benign
0.42
T
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
T
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.

Other links and lift over

dbSNP: rs781714195; hg19: chr1-68962670; API