Variant 12-31590801-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144973.4(DENND5B):c.32G>T(p.Gly11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,315,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

DENND5B
NM_144973.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.286

Variant links:

Genes affected

DENND5B (HGNC:28338): (DENN domain containing 5B) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in positive regulation of triglyceride transport and regulation of catalytic activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

DENND5B links:

DENND5B (HGNC:):

DENND5B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14195177).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND5B	NM_144973.4 linkuse as main transcript	c.32G>T	p.Gly11Val	missense_variant	1/21	ENST00000389082.10	NP_659410.3	Q6ZUT9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND5B	ENST00000389082.10 linkuse as main transcript	c.32G>T	p.Gly11Val	missense_variant	1/21	5	NM_144973.4	ENSP00000373734.5		Q6ZUT9-1

Frequencies

GnomAD3 genomes

AF:

0.0000528

AC:

AN:

151582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000119

AC:

138

AN:

1163612

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

564304

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.000128

GnomAD4 genome

AF:

0.0000528

AC:

AN:

151582

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 03, 2022

The c.32G>T (p.G11V) alteration is located in exon 1 (coding exon 1) of the DENND5B gene. This alteration results from a G to T substitution at nucleotide position 32, causing the glycine (G) at amino acid position 11 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.54

T;T

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

L;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.88

N;N

REVEL

Benign

0.013

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.031

D;D

Polyphen

0.014

B;P

Vest4

0.23

MutPred

0.21

Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);

MVP

0.082

MPC

0.67

ClinPred

0.78

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.16

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.

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