NM_130443.4:c.167C>A

Variant names:

• chr11-66482367-C-A
• rs1247011196
• NM_130443.4:c.167C>A

Variant summary

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

The NM_130443.4(DPP3):​c.167C>A​(p.Ala56Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,362 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A56V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DPP3 NM_130443.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.35
• Publications: 1 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.167C>A	p.Ala56Asp	missense	Exon 2 of 18	NP_569710.2	Q9NY33-1
	DPP3	NM_005700.5		c.167C>A	p.Ala56Asp	missense	Exon 2 of 18	NP_005691.2
	DPP3	NM_001256670.2		c.167C>A	p.Ala56Asp	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.167C>A	p.Ala56Asp	missense	Exon 2 of 18	ENSP00000432782.2	Q9NY33-1
	DPP3	ENST00000532677.5	TSL:1	c.224C>A	p.Ala75Asp	missense	Exon 2 of 18	ENSP00000435284.1	G3V1D3
	DPP3	ENST00000883964.1		c.167C>A	p.Ala56Asp	missense	Exon 2 of 18	ENSP00000554023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250108 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460362 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726614

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.3
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.94	P
Vest4		0.78
MutPred		0.53		Gain of phosphorylation at Y77 (P = 0.0734)
MVP		0.76
ClinPred		0.81	D
GERP RS		5.8
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.62
Mutation Taster		=26/74	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

dbSNP: rs1247011196; hg19: chr11-66249838;