chr8-141150965-C-T

Position:

• chr8-141150965-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352890.3(DENND3):​c.855+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,519,972 control chromosomes in the GnomAD database, including 83,796 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7271 hom., cov: 34)
  • Exomes 𝑓: 0.33 (76525 hom.)
• Consequence: DENND3 NM_001352890.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND3	NM_001352890.3	c.855+12C>T		intron_variant		ENST00000519811.6	NP_001339819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND3	ENST00000519811.6	c.855+12C>T		intron_variant		5	NM_001352890.3	ENSP00000428714.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46354 AN: 152110 Hom.: 7273 Cov.: 34

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.298

GnomAD3 exomes AF: 0.334 AC: 59472 AN: 178066 Hom.: 10052 AF XY: 0.337 AC XY: 32549 AN XY: 96496

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.211

Gnomad SAS exome AF: 0.326

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.357

Gnomad OTH exome AF: 0.361

GnomAD4 exome AF: 0.332 AC: 454324 AN: 1367744 Hom.: 76525 Cov.: 33 AF XY: 0.332 AC XY: 223723 AN XY: 674826

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.305 AC: 46363 AN: 152228 Hom.: 7271 Cov.: 34 AF XY: 0.302 AC XY: 22486 AN XY: 74440

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.297

Alfa AF: 0.327 Hom.: 10370

Bravo AF: 0.293

Asia WGS AF: 0.243 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.053
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs3816063; hg19: chr8-142161064; COSMIC: COSV52805765; COSMIC: COSV52805765;