Variant 12-31398335-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_144973.4(DENND5B):c.3096A>G(p.Lys1032Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,550,408 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 12 hom. )

Consequence

DENND5B
NM_144973.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 12-31398335-T-C is Benign according to our data. Variant chr12-31398335-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642826.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BS2

High AC in GnomAd4 at 310 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND5B	NM_144973.4 link	c.3096A>G	p.Lys1032Lys	synonymous_variant	17/21	ENST00000389082.10	NP_659410.3	Q6ZUT9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND5B	ENST00000389082.10 link	c.3096A>G	p.Lys1032Lys	synonymous_variant	17/21	5	NM_144973.4	ENSP00000373734.5		Q6ZUT9-1
DENND5B	ENST00000536562.5 link	c.3201A>G	p.Lys1067Lys	synonymous_variant	19/23	2		ENSP00000444889.1		G3V1S3

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00773

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00293

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00235

AC:

363

AN:

154774

Hom.:

AF XY:

0.00217

AC XY:

178

AN XY:

81914

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.000518

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00808

Gnomad NFE exome

AF:

0.00320

Gnomad OTH exome

AF:

0.00322

GnomAD4 exome

AF:

0.00308

AC:

4304

AN:

1398186

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

1998

AN XY:

689674

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000487

Gnomad4 ASJ exome

AF:

0.000159

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00806

Gnomad4 NFE exome

AF:

0.00342

Gnomad4 OTH exome

AF:

0.00312

GnomAD4 genome

AF:

0.00204

AC:

310

AN:

152222

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00773

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00236

Hom.:

Bravo

AF:

0.00154

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

DENND5B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.1

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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