Variant chr8-141144160-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001352890.3(DENND3):c.636T>A(p.Leu212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,611,200 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 20 hom. )

Consequence

DENND3
NM_001352890.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.842

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 8-141144160-T-A is Benign according to our data. Variant chr8-141144160-T-A is described in ClinVar as [Benign]. Clinvar id is 715620.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.842 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00765 (1165/152346) while in subpopulation AFR AF= 0.0267 (1111/41582). AF 95% confidence interval is 0.0254. There are 18 homozygotes in gnomad4. There are 532 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND3	NM_001352890.3 linkuse as main transcript	c.636T>A	p.Leu212=	synonymous_variant	5/23	ENST00000519811.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND3	ENST00000519811.6 linkuse as main transcript	c.636T>A	p.Leu212=	synonymous_variant	5/23	5	NM_001352890.3	P2

Frequencies

GnomAD3 genomes

AF:

0.00766

AC:

1166

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

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:

0.000132

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00212

AC:

525

AN:

248206

Hom.:

AF XY:

0.00161

AC XY:

216

AN XY:

134138

show subpopulations

Gnomad AFR exome

AF:

0.0281

Gnomad AMR exome

AF:

0.00161

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000675

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000658

GnomAD4 exome

AF:

0.000853

AC:

1244

AN:

1458854

Hom.:

Cov.:

AF XY:

0.000726

AC XY:

527

AN XY:

725672

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000938

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000909

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00765

AC:

1165

AN:

152346

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

532

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0267

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00241

Hom.:

Bravo

AF:

0.00867

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jul 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.56

DANN

Benign

0.71

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