8-141155934-A-T

Variant names:

• chr8-141155934-A-T
• NM_001352890.3:c.1160A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001352890.3(DENND3):​c.1160A>T​(p.Asp387Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,064 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DENND3 NM_001352890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND3	NM_001352890.3	c.1160A>T	p.Asp387Val	missense_variant	Exon 8 of 23	ENST00000519811.6	NP_001339819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND3	ENST00000519811.6	c.1160A>T	p.Asp387Val	missense_variant	Exon 8 of 23	5	NM_001352890.3	ENSP00000428714.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460064 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.2	M;.;M
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.016	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.97	D;D;.
Vest4		0.61
MutPred		0.42		.;Loss of disorder (P = 0.0668);.;
MVP		0.26
MPC		1.5
ClinPred		0.76	D
GERP RS		1.2
Varity_R		0.16
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-142166033;