chr10-119115358-G-C

Position:

• chr10-119115358-G-C

Variant summary

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

The NM_207009.4(DENND10):​c.333-2161G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 138,046 control chromosomes in the GnomAD database, including 21,448 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 0.54 (21448 hom., cov: 22)
• Consequence: DENND10 NM_207009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

Genes affected

DENND10 (HGNC:31793): (DENN domain containing 10) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endosome transport via multivesicular body sorting pathway; protein transport; and regulation of early endosome to late endosome transport. Located in late endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND10	NM_207009.4	c.333-2161G>C		intron_variant		ENST00000361432.3	NP_996892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND10	ENST00000361432.3	c.333-2161G>C		intron_variant		1	NM_207009.4	ENSP00000354688	P1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 74766 AN: 137942 Hom.: 21440 Cov.: 22

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.587

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.542 AC: 74804 AN: 138046 Hom.: 21448 Cov.: 22 AF XY: 0.541 AC XY: 35752 AN XY: 66122

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.589

Alfa AF: 0.413 Hom.: 1099

Bravo AF: 0.549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.52

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: rs11198783; hg19: chr10-120874870;