5-60603522-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018369.3(DEPDC1B):​c.1111G>A​(p.Val371Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000932 in 1,608,856 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

DEPDC1B
NM_018369.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77
Variant links:
Genes affected
DEPDC1B (HGNC:24902): (DEP domain containing 1B) Predicted to enable GTPase activator activity. Involved in cell migration and positive regulation of Wnt signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0758636).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DEPDC1BNM_018369.3 linkc.1111G>A p.Val371Met missense_variant Exon 9 of 11 ENST00000265036.10 NP_060839.2 Q8WUY9-1
DEPDC1BNM_001145208.2 linkc.1111G>A p.Val371Met missense_variant Exon 9 of 10 NP_001138680.1 Q8WUY9-2
DEPDC1BXM_011543509.3 linkc.1066G>A p.Val356Met missense_variant Exon 9 of 11 XP_011541811.1
DEPDC1BXM_047417369.1 linkc.1066G>A p.Val356Met missense_variant Exon 9 of 10 XP_047273325.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DEPDC1BENST00000265036.10 linkc.1111G>A p.Val371Met missense_variant Exon 9 of 11 1 NM_018369.3 ENSP00000265036.5 Q8WUY9-1
DEPDC1BENST00000453022.6 linkc.1111G>A p.Val371Met missense_variant Exon 9 of 10 2 ENSP00000389101.2 Q8WUY9-2
DEPDC1BENST00000512078.5 linkn.*1108G>A non_coding_transcript_exon_variant Exon 10 of 11 2 ENSP00000427527.1 D6RIB0
DEPDC1BENST00000512078.5 linkn.*1108G>A 3_prime_UTR_variant Exon 10 of 11 2 ENSP00000427527.1 D6RIB0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152092
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
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:
0.0000327
AC:
8
AN:
244670
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132172
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000443
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:
0.00000961
AC:
14
AN:
1456646
Hom.:
0
Cov.:
30
AF XY:
0.00000828
AC XY:
6
AN XY:
724568
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000354
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1111G>A (p.V371M) alteration is located in exon 9 (coding exon 9) of the DEPDC1B gene. This alteration results from a G to A substitution at nucleotide position 1111, causing the valine (V) at amino acid position 371 to be replaced by a methionine (M). 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
0.16
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.062
T;.
Eigen
Benign
-0.14
Eigen_PC
Benign
0.048
FATHMM_MKL
Benign
0.65
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.076
T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
0.72
N;N
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.23
Sift
Benign
0.18
T;T
Sift4G
Benign
0.14
T;T
Polyphen
0.11
B;.
Vest4
0.27
MVP
0.85
MPC
0.18
ClinPred
0.13
T
GERP RS
5.3
Varity_R
0.10
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
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.

Other links and lift over

dbSNP: rs201218269; hg19: chr5-59899349; COSMIC: COSV54008815; COSMIC: COSV54008815; API