chr8-141165223-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001352890.3(DENND3):​c.1487C>T​(p.Ala496Val) variant causes a missense change. The variant allele was found at a frequency of 0.00024 in 1,614,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

DENND3
NM_001352890.3 missense

Scores

1
7
11

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.68
Variant links:
Genes affected
DENND3 (HGNC:29134): (DENN domain containing 3) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in cellular protein catabolic process; endosome to lysosome transport; and regulation of Rab protein signal transduction. Predicted to be located in cytosol. Predicted to be active in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.013235807).
BP6
Variant 8-141165223-C-T is Benign according to our data. Variant chr8-141165223-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 712479.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DENND3NM_001352890.3 linkuse as main transcriptc.1487C>T p.Ala496Val missense_variant 11/23 ENST00000519811.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DENND3ENST00000519811.6 linkuse as main transcriptc.1487C>T p.Ala496Val missense_variant 11/235 NM_001352890.3 P2

Frequencies

GnomAD3 genomes
AF:
0.00132
AC:
201
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00425
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
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:
0.000338
AC:
85
AN:
251492
Hom.:
0
AF XY:
0.000346
AC XY:
47
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00418
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000125
AC:
183
AN:
1461848
Hom.:
0
Cov.:
30
AF XY:
0.000124
AC XY:
90
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00439
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.00134
AC:
204
AN:
152320
Hom.:
0
Cov.:
32
AF XY:
0.00138
AC XY:
103
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00431
Gnomad4 AMR
AF:
0.00163
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:
0.000203
Hom.:
0
Bravo
AF:
0.00146
ESP6500AA
AF:
0.00318
AC:
14
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000379
AC:
46
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 19, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.18
T;.;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.013
T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.8
L;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.3
N;N;N
REVEL
Benign
0.19
Sift
Benign
0.087
T;T;T
Sift4G
Uncertain
0.047
D;D;D
Polyphen
0.99
D;D;D
Vest4
0.46
MVP
0.48
MPC
1.3
ClinPred
0.053
T
GERP RS
5.4
Varity_R
0.16
gMVP
0.32

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: rs145045660; hg19: chr8-142175322; API