11-66482282-C-T

Variant names:

• chr11-66482282-C-T
• NM_130443.4:c.82C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130443.4(DPP3):​c.82C>T​(p.Pro28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPP3 NM_130443.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19891104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP3	NM_130443.4	c.82C>T	p.Pro28Ser	missense_variant	Exon 2 of 18	ENST00000531863.6	NP_569710.2
DPP3	NM_005700.5	c.82C>T	p.Pro28Ser	missense_variant	Exon 2 of 18		NP_005691.2
DPP3	NM_001256670.2	c.82C>T	p.Pro28Ser	missense_variant	Exon 2 of 17		NP_001243599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP3	ENST00000531863.6	c.82C>T	p.Pro28Ser	missense_variant	Exon 2 of 18	1	NM_130443.4	ENSP00000432782.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.82C>T (p.P28S) alteration is located in exon 2 (coding exon 1) of the DPP3 gene. This alteration results from a C to T substitution at nucleotide position 82, causing the proline (P) at amino acid position 28 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T;T;T;T;.;T;.
Eigen	Benign	-0.077
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T;T;T;T;T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;.;L;.;L;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.38	T;T;T;T;T;T;T
Sift4G	Benign	0.54	T;T;T;D;T;T;T
Polyphen		0.38, 0.0060	.;B;B;.;.;.;.
Vest4		0.17
MutPred		0.29		.;Gain of helix (P = 0.062);.;.;.;.;.;
MVP		0.54
ClinPred		0.53	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-66249753;