rs201037983

Variant summary

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

The NM_014856.3(DENND4B):​c.3785G>C​(p.Gly1262Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,566 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1262E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

DENND4B
NM_014856.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44
Variant links:
Genes affected
DENND4B (HGNC:29044): (DENN domain containing 4B) Enables guanyl-nucleotide exchange factor activity. Involved in regulation of Rab protein signal transduction. Located in Golgi apparatus and nucleoplasm. [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=0.087699056).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DENND4BNM_014856.3 linkc.3785G>C p.Gly1262Ala missense_variant Exon 24 of 28 ENST00000361217.9 NP_055671.2 O75064

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DENND4BENST00000361217.9 linkc.3785G>C p.Gly1262Ala missense_variant Exon 24 of 28 1 NM_014856.3 ENSP00000354597.4 O75064

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000822
AC:
2
AN:
243218
Hom.:
0
AF XY:
0.0000151
AC XY:
2
AN XY:
132142
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000665
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459566
Hom.:
0
Cov.:
32
AF XY:
0.00000276
AC XY:
2
AN XY:
725866
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000826
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
18
DANN
Benign
0.55
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.088
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.90
L
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.21
N
REVEL
Benign
0.095
Sift
Benign
0.065
T
Sift4G
Benign
0.99
T
Polyphen
0.30
B
Vest4
0.30
MutPred
0.29
Gain of helix (P = 0.0164);
MVP
0.068
MPC
1.8
ClinPred
0.12
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.049
gMVP
0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201037983; hg19: chr1-153904891; API