11-66482244-C-A

Variant names:

• chr11-66482244-C-A
• rs200192681
• NM_130443.4:c.44C>A

Variant summary

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

The NM_130443.4(DPP3):​c.44C>A​(p.Ser15Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S15C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPP3 NM_130443.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87

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=0.21493798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP3	NM_130443.4	c.44C>A	p.Ser15Tyr	missense_variant	Exon 2 of 18	ENST00000531863.6	NP_569710.2
DPP3	NM_005700.5	c.44C>A	p.Ser15Tyr	missense_variant	Exon 2 of 18		NP_005691.2
DPP3	NM_001256670.2	c.44C>A	p.Ser15Tyr	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.44C>A	p.Ser15Tyr	missense_variant	Exon 2 of 18	1	NM_130443.4	ENSP00000432782.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.0046	T;T;T;T;.;T;.
Eigen	Benign	-0.089
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;.;L;.;L;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.34	N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T;T;D;T;T;T
Sift4G	Benign	0.94	T;T;T;D;T;D;T
Polyphen		0.016, 0.0030	.;B;B;.;.;.;.
Vest4		0.55
MutPred		0.52		.;Gain of catalytic residue at S34 (P = 0.092);.;.;.;.;.;
MVP		0.64
ClinPred		0.38	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs200192681; hg19: chr11-66249715;