Variant 8-141150824-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001352890.3(DENND3):c.736-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 1,587,276 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 52 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 48 hom. )

Consequence

DENND3
NM_001352890.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0005587

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.445

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-141150824-G-A is Benign according to our data. Variant chr8-141150824-G-A is described in ClinVar as [Benign]. Clinvar id is 783536.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 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.736-10G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000519811.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND3	ENST00000519811.6 linkuse as main transcript	c.736-10G>A		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001352890.3	P2

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2277

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0517

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00390

AC:

880

AN:

225810

Hom.:

AF XY:

0.00300

AC XY:

368

AN XY:

122536

show subpopulations

Gnomad AFR exome

AF:

0.0521

Gnomad AMR exome

AF:

0.00204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000768

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000287

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00149

AC:

2137

AN:

1434926

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

963

AN XY:

713360

show subpopulations

Gnomad4 AFR exome

AF:

0.0549

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000171

Gnomad4 FIN exome

AF:

0.0000379

Gnomad4 NFE exome

AF:

0.0000399

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.0150

AC:

2286

AN:

152350

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1066

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0518

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00941

Hom.:

Bravo

AF:

0.0171

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.7

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00056

dbscSNV1_RF

Benign

0.032

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.

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