11-66482417-G-C

Variant names:

• chr11-66482417-G-C
• rs536918372
• NM_130443.4:c.217G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_130443.4(DPP3):​c.217G>C​(p.Asp73His) variant causes a missense change. The variant allele was found at a frequency of 0.0000117 in 1,457,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D73N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: DPP3 NM_130443.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.397453).

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.217G>C	p.Asp73His	missense	Exon 2 of 18	NP_569710.2	Q9NY33-1
	DPP3	NM_005700.5		c.217G>C	p.Asp73His	missense	Exon 2 of 18	NP_005691.2
	DPP3	NM_001256670.2		c.217G>C	p.Asp73His	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.217G>C	p.Asp73His	missense	Exon 2 of 18	ENSP00000432782.2	Q9NY33-1
	DPP3	ENST00000532677.5	TSL:1	c.274G>C	p.Asp92His	missense	Exon 2 of 18	ENSP00000435284.1	G3V1D3
	DPP3	ENST00000883964.1		c.217G>C	p.Asp73His	missense	Exon 2 of 18	ENSP00000554023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247636 AF XY: 0.00

Gnomad AFR exome AF: 0.0000618

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: 0.0000117 AC: 17 AN: 1457160 Hom.: 0 Cov.: 31 AF XY: 0.00000965 AC XY: 7 AN XY: 725132

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48758

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111992

Other (OTH) AF: 0.000149 AC: 9 AN: 60360

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.098
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.014	D
Polyphen		0.92	P
Vest4		0.34
MutPred		0.35		Loss of helix (P = 0.0304)
MVP		0.65
ClinPred		0.94	D
GERP RS		5.6
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.38
Mutation Taster		=73/27	polymorphism

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: rs536918372; hg19: chr11-66249888;