rs10986105

Variant names:

• chr9-123787676-T-G
• rs10986105
• NM_001352964.2:c.132+4911A>C

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+4911A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 152,188 control chromosomes in the GnomAD database, including 482 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 (482 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 23 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=-0.25).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.132+4911A>C		intron_variant	Intron 3 of 23	ENST00000394215.7	NP_001339893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1A	ENST00000394215.7	c.132+4911A>C		intron_variant	Intron 3 of 23	5	NM_001352964.2	ENSP00000377763.4

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10425 AN: 152070 Hom.: 482 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0518

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0623

Gnomad EAS AF: 0.0537

Gnomad SAS AF: 0.0669

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.0713

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

GnomAD4 genome AF: 0.0685 AC: 10426 AN: 152188 Hom.: 482 Cov.: 32 AF XY: 0.0699 AC XY: 5202 AN XY: 74426

African (AFR) AF: 0.132 AC: 5470 AN: 41514

American (AMR) AF: 0.0567 AC: 867 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0623 AC: 216 AN: 3468

East Asian (EAS) AF: 0.0538 AC: 279 AN: 5182

South Asian (SAS) AF: 0.0671 AC: 324 AN: 4826

European-Finnish (FIN) AF: 0.0560 AC: 594 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0363 AC: 2468 AN: 67994

Other (OTH) AF: 0.0705 AC: 149 AN: 2112

Alfa AF: 0.0585 Hom.: 52

Bravo AF: 0.0726

Asia WGS AF: 0.0480 AC: 167 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		2.0
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

Other links and lift over

dbSNP: rs10986105; hg19: chr9-126549955;