9-123381909-TGG-GGT

Variant names:

• chr9-123381909-TGG-GGT
• NM_001352964.2:c.2734_2736delCCAinsACC
• DENND1A p.Pro912Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001352964.2(DENND1A):​c.2734_2736delCCAinsACC​(p.Pro912Thr) variant causes a missense change. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: DENND1A NM_001352964.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.2734_2736delCCAinsACC	p.Pro912Thr	missense	N/A	NP_001339893.1	A0A0A0MS48
	DENND1A	NM_001393654.1		c.2680_2682delCCAinsACC	p.Pro894Thr	missense	N/A	NP_001380583.1
	DENND1A	NM_001352965.2		c.2584_2586delCCAinsACC	p.Pro862Thr	missense	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.2734_2736delCCAinsACC	p.Pro912Thr	missense	N/A	ENSP00000377763.4	A0A0A0MS48
	DENND1A	ENST00000473039.5	TSL:1	n.2543_2545delCCAinsACC		non_coding_transcript_exon	Exon 18 of 18
	DENND1A	ENST00000866226.1		c.2680_2682delCCAinsACC	p.Pro894Thr	missense	N/A	ENSP00000536285.1

Frequencies

GnomAD3 genomes Cov.: 0

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

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9

Splicing

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

hg19: chr9-126144188;