NM_001352890.3:c.736-10G>A

Variant names:

• chr8-141150824-G-A
• rs73362440
• NM_001352890.3:c.736-10G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001352890.3(DENND3):​c.736-10G>A variant causes a 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 intron
• Scores: Splicing: ADA: 0.0005587
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.445
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352890.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND3	NM_001352890.3	MANE Select	c.736-10G>A		intron	N/A	NP_001339819.2	E9PF32
	DENND3	NM_001362798.2		c.736-10G>A		intron	N/A	NP_001349727.1
	DENND3	NM_014957.5		c.535-10G>A		intron	N/A	NP_055772.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND3	ENST00000519811.6	TSL:5 MANE Select	c.736-10G>A		intron	N/A	ENSP00000428714.1	E9PF32
	DENND3	ENST00000424248.2	TSL:1	c.496-10G>A		intron	N/A	ENSP00000410594.1	A2RUS2-2
	DENND3	ENST00000885117.1		c.736-10G>A		intron	N/A	ENSP00000555176.1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2277 AN: 152232 Hom.: 53 Cov.: 33

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

GnomAD2 exomes AF: 0.00390 AC: 880 AN: 225810 AF XY: 0.00300

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 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.: 48 Cov.: 30 AF XY: 0.00135 AC XY: 963 AN XY: 713360

African (AFR) AF: 0.0549 AC: 1769 AN: 32240

American (AMR) AF: 0.00259 AC: 100 AN: 38566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24630

East Asian (EAS) AF: 0.00 AC: 0 AN: 38656

South Asian (SAS) AF: 0.000171 AC: 14 AN: 81792

European-Finnish (FIN) AF: 0.0000379 AC: 2 AN: 52748

Middle Eastern (MID) AF: 0.00265 AC: 15 AN: 5652

European-Non Finnish (NFE) AF: 0.0000399 AC: 44 AN: 1101426

Other (OTH) AF: 0.00326 AC: 193 AN: 59216

GnomAD4 genome AF: 0.0150 AC: 2286 AN: 152350 Hom.: 52 Cov.: 33 AF XY: 0.0143 AC XY: 1066 AN XY: 74498

African (AFR) AF: 0.0518 AC: 2152 AN: 41584

American (AMR) AF: 0.00588 AC: 90 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68030

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.00870 Hom.: 19

Bravo AF: 0.0171

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.56
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73362440; hg19: chr8-142160923; COSMIC: COSV105005225;