rs12348586

Variant names:

• chr9-123399109-A-C
• rs12348586
• NM_001352964.2:c.1631+4293T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-123399109-A-C
• chr9-123399109-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352964.2(DENND1A):​c.1631+4293T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,938 control chromosomes in the GnomAD database, including 1,415 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 0.13 (1415 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.176 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.1631+4293T>G		intron	N/A	NP_001339893.1	A0A0A0MS48
	DENND1A	NM_001393654.1		c.1577+4293T>G		intron	N/A	NP_001380583.1
	DENND1A	NM_001352965.2		c.1481+4293T>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.1631+4293T>G		intron	N/A	ENSP00000377763.4	A0A0A0MS48
	DENND1A	ENST00000473039.5	TSL:1	n.1440+4293T>G		intron	N/A
	DENND1A	ENST00000866226.1		c.1577+4293T>G		intron	N/A	ENSP00000536285.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20378 AN: 151820 Hom.: 1405 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.134 AC: 20409 AN: 151938 Hom.: 1415 Cov.: 32 AF XY: 0.139 AC XY: 10286 AN XY: 74230

African (AFR) AF: 0.130 AC: 5389 AN: 41434

American (AMR) AF: 0.182 AC: 2772 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 200 AN: 3464

East Asian (EAS) AF: 0.0910 AC: 469 AN: 5152

South Asian (SAS) AF: 0.133 AC: 640 AN: 4806

European-Finnish (FIN) AF: 0.192 AC: 2022 AN: 10556

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.125 AC: 8464 AN: 67940

Other (OTH) AF: 0.141 AC: 298 AN: 2112

Alfa AF: 0.126 Hom.: 656

Bravo AF: 0.134

Asia WGS AF: 0.0950 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.77
PhyloP100		0.51
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs12348586; hg19: chr9-126161388;