dbSNP rs12421620: DPP3:p.Glu690Lys (chr11-66509105-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_130443.4(DPP3):c.2068G>A(p.Glu690Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0293 in 1,613,996 control chromosomes in the GnomAD database, including 4,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.037 ( 537 hom., cov: 32)

Exomes 𝑓: 0.029 ( 4137 hom. )

Consequence

DPP3
NM_130443.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.55

Variant links:

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]

DPP3 links:

ENSG00000256349 (HGNC:):

ENSG00000256349 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016162097).

BP6

Variant 11-66509105-G-A is Benign according to our data. Variant chr11-66509105-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP3	NM_130443.4 link	c.2068G>A	p.Glu690Lys	missense_variant	Exon 18 of 18	ENST00000531863.6	NP_569710.2	Q9NY33-1Q5JPB8
DPP3	NM_005700.5 link	c.2068G>A	p.Glu690Lys	missense_variant	Exon 18 of 18		NP_005691.2	Q9NY33-1
DPP3	NM_001256670.2 link	c.1978G>A	p.Glu660Lys	missense_variant	Exon 17 of 17		NP_001243599.1	Q9NY33-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP3	ENST00000531863.6 link	c.2068G>A	p.Glu690Lys	missense_variant	Exon 18 of 18	1	NM_130443.4	ENSP00000432782.2		Q9NY33-1G3V180
ENSG00000256349	ENST00000419755 link	c.-52G>A		5_prime_UTR_variant	Exon 1 of 17	2		ENSP00000398526.3

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5616

AN:

152098

Hom.:

538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00763

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.0616

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0729

AC:

18316

AN:

251146

Hom.:

3272

AF XY:

0.0584

AC XY:

7933

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00733

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.00596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0169

Gnomad FIN exome

AF:

0.0613

Gnomad NFE exome

AF:

0.0178

Gnomad OTH exome

AF:

0.0610

GnomAD4 exome

AF:

0.0285

AC:

41684

AN:

1461780

Hom.:

4137

Cov.:

AF XY:

0.0264

AC XY:

19230

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00523

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.00696

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0173

Gnomad4 FIN exome

AF:

0.0613

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0369

AC:

5618

AN:

152216

Hom.:

537

Cov.:

AF XY:

0.0419

AC XY:

3120

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00760

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0155

Gnomad4 FIN

AF:

0.0616

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0341

Alfa

AF:

0.0203

Hom.:

291

Bravo

AF:

0.0524

TwinsUK

AF:

0.0170

AC:

ALSPAC

AF:

0.0150

AC:

ESP6500AA

AF:

0.00750

AC:

ESP6500EA

AF:

0.0178

AC:

153

ExAC

AF:

0.0586

AC:

7117

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0150

EpiControl

AF:

0.0137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

T;T;T;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

D;D;D;D

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.6

D;D;D;D

REVEL

Benign

0.17

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.60, 0.52

.;P;P;.

Vest4

0.17

ClinPred

0.019

GERP RS

5.3

Varity_R

0.63

gMVP

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over