rs10818872

Variant names:

• chr9-123789497-T-C
• rs10818872
• NM_001352964.2:c.132+3090A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001352964.2(DENND1A):​c.132+3090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 152,162 control chromosomes in the GnomAD database, including 489 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 0.069 (489 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39
• Publications: 3 publications found

Genes affected

DENND1A (HGNC:29324): (DENN domain containing 1A) Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1A, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352964.2. 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
	DENND1A	NM_001352964.2	MANE Select	c.132+3090A>G		intron	N/A	NP_001339893.1	A0A0A0MS48
	DENND1A	NM_001393654.1		c.132+3090A>G		intron	N/A	NP_001380583.1
	DENND1A	NM_001352965.2		c.37-19934A>G		intron	N/A	NP_001339894.1	Q8TEH3-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND1A	ENST00000394215.7	TSL:5 MANE Select	c.132+3090A>G		intron	N/A	ENSP00000377763.4	A0A0A0MS48
	DENND1A	ENST00000373620.7	TSL:1	c.132+3090A>G		intron	N/A	ENSP00000362722.3	Q8TEH3-2
	DENND1A	ENST00000373618.1	TSL:1	c.86+3090A>G		intron	N/A	ENSP00000362720.1	Q8TEH3-4

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10452 AN: 152044 Hom.: 489 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0687 AC: 10452 AN: 152162 Hom.: 489 Cov.: 32 AF XY: 0.0701 AC XY: 5216 AN XY: 74400

African (AFR) AF: 0.132 AC: 5498 AN: 41498

American (AMR) AF: 0.0569 AC: 869 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 216 AN: 3470

East Asian (EAS) AF: 0.0532 AC: 276 AN: 5186

South Asian (SAS) AF: 0.0674 AC: 325 AN: 4824

European-Finnish (FIN) AF: 0.0560 AC: 594 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0363 AC: 2465 AN: 67976

Other (OTH) AF: 0.0705 AC: 149 AN: 2114

Alfa AF: 0.0484 Hom.: 131

Bravo AF: 0.0728

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.83
PhyloP100		3.4
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10818872;

hg19: chr9-126551776;