NM_130443.4:c.32A>G

Variant names:

• chr11-66482232-A-G
• NM_130443.4:c.32A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_130443.4(DPP3):​c.32A>G​(p.Asp11Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPP3 NM_130443.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.78
• Publications: 0 publications found

Genes affected

DPP3 (HGNC:3008): (dipeptidyl peptidase 3) This gene encodes a protein that is a member of the M49 family of metallopeptidases. This cytoplasmic protein binds a single zinc ion with its zinc-binding motif (HELLGH) and has post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Increased activity of this protein is associated with endometrial and ovarian cancers. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130443.4. 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
	DPP3	NM_130443.4	MANE Select	c.32A>G	p.Asp11Gly	missense	Exon 2 of 18	NP_569710.2	Q9NY33-1
	DPP3	NM_005700.5		c.32A>G	p.Asp11Gly	missense	Exon 2 of 18	NP_005691.2
	DPP3	NM_001256670.2		c.32A>G	p.Asp11Gly	missense	Exon 2 of 17	NP_001243599.1	Q9NY33-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP3	ENST00000531863.6	TSL:1 MANE Select	c.32A>G	p.Asp11Gly	missense	Exon 2 of 18	ENSP00000432782.2	Q9NY33-1
	DPP3	ENST00000532677.5	TSL:1	c.89A>G	p.Asp30Gly	missense	Exon 2 of 18	ENSP00000435284.1	G3V1D3
	DPP3	ENST00000883964.1		c.32A>G	p.Asp11Gly	missense	Exon 2 of 18	ENSP00000554023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.029	D
Sift4G	Benign	0.14	T
Polyphen		0.57	P
Vest4		0.69
MutPred		0.53		Loss of stability (P = 0.0222)
MVP		0.72
ClinPred		0.99	D
GERP RS		5.7
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.50
Mutation Taster		=43/57	disease causing

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

hg19: chr11-66249703;