Genetic Variant NM_130443.4:c.2068G>A (chr11-66509105-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

13 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

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

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DPP3	NM_130443.4	MANE Select	c.2068G>A	p.Glu690Lys	missense	Exon 18 of 18	NP_569710.2
DPP3	NM_005700.5		c.2068G>A	p.Glu690Lys	missense	Exon 18 of 18	NP_005691.2
DPP3	NM_001256670.2		c.1978G>A	p.Glu660Lys	missense	Exon 17 of 17	NP_001243599.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DPP3	ENST00000531863.6	TSL:1 MANE Select	c.2068G>A	p.Glu690Lys	missense	Exon 18 of 18	ENSP00000432782.2
DPP3	ENST00000532677.5	TSL:1	c.2125G>A	p.Glu709Lys	missense	Exon 18 of 18	ENSP00000435284.1
ENSG00000256349	ENST00000419755.3	TSL:2	c.-52G>A		5_prime_UTR	Exon 1 of 17	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

GnomAD2 exomes

AF:

0.0729

AC:

18316

AN:

251146

AF XY:

0.0584

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 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

African (AFR)

AF:

0.00523

AC:

175

AN:

33472

American (AMR)

AF:

0.382

AC:

17095

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00696

AC:

182

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0173

AC:

1493

AN:

86254

European-Finnish (FIN)

AF:

0.0613

AC:

3270

AN:

53362

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0161

AC:

17853

AN:

1111984

Other (OTH)

AF:

0.0257

AC:

1554

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

2048

4096

6143

8191

10239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

826

1652

2478

3304

4130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0369

AC:

5618

AN:

152216

Hom.:

537

Cov.:

AF XY:

0.0419

AC XY:

3120

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00760

AC:

316

AN:

41554

American (AMR)

AF:

0.216

AC:

3305

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0155

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0616

AC:

652

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0172

AC:

1170

AN:

68018

Other (OTH)

AF:

0.0341

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

230

459

689

918

1148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0231

Hom.:

815

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

PhyloP100

6.6

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.17

Sift

Benign

0.11

Sift4G

Benign

0.11

Polyphen

0.60

Vest4

0.17

ClinPred

0.019

GERP RS

5.3

PromoterAI

0.0015

Neutral

(source)

Varity_R

0.63

gMVP

0.79

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over