Variant 8-141160785-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001352890.3(DENND3):c.1350C>T(p.Phe450=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,607,108 control chromosomes in the GnomAD database, including 84,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.28 ( 6273 hom., cov: 33)

Exomes 𝑓: 0.32 ( 78414 hom. )

Consequence

DENND3
NM_001352890.3 splice_region, synonymous

Scores

Splicing: ADA: 0.9792

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.86

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]

DENND3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND3	NM_001352890.3 linkuse as main transcript	c.1350C>T	p.Phe450=	splice_region_variant, synonymous_variant	9/23	ENST00000519811.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND3	ENST00000519811.6 linkuse as main transcript	c.1350C>T	p.Phe450=	splice_region_variant, synonymous_variant	9/23	5	NM_001352890.3	P2

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

42025

AN:

151994

Hom.:

6276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.303

GnomAD3 exomes

AF:

0.336

AC:

82782

AN:

246562

Hom.:

14655

AF XY:

0.342

AC XY:

45835

AN XY:

134162

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.412

Gnomad ASJ exome

AF:

0.296

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.456

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.323

AC:

470374

AN:

1454996

Hom.:

78414

Cov.:

AF XY:

0.327

AC XY:

236614

AN XY:

722612

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.407

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.373

Gnomad4 SAS exome

AF:

0.461

Gnomad4 FIN exome

AF:

0.288

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.319

GnomAD4 genome

AF:

0.276

AC:

42027

AN:

152112

Hom.:

6273

Cov.:

AF XY:

0.281

AC XY:

20893

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.287

Gnomad4 EAS

AF:

0.332

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.289

Gnomad4 NFE

AF:

0.307

Gnomad4 OTH

AF:

0.308

Alfa

AF:

0.306

Hom.:

15602

Bravo

AF:

0.276

Asia WGS

AF:

0.360

AC:

1253

AN:

3478

EpiCase

AF:

0.305

EpiControl

AF:

0.311

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Aganglionic megacolon

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Clinical Genetics, Erasmus University Medical Center

May 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Benign

0.71

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