Genetic Variant NM_139159.5:c.1855C>T (chr19-4688787-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139159.5(DPP9):c.1855C>T(p.Arg619Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,469,582 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: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

DPP9
NM_139159.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Variant links:

Genes affected

DPP9 (HGNC:18648): (dipeptidyl peptidase 9) This gene encodes a protein that is a member of the S9B family in clan SC of the serine proteases. The protein has been shown to have post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Although the activity of this protein is similar to that of dipeptidyl peptidase 4 (DPP4), it does not appear to be membrane bound. In general, dipeptidyl peptidases appear to be involved in the regulation of the activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. Several transcript variants of this gene have been described but not fully characterized. [provided by RefSeq, Jul 2008]

DPP9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.16624805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP9	NM_139159.5 link	c.1855C>T	p.Arg619Cys	missense_variant	Exon 16 of 22	ENST00000262960.14	NP_631898.3	Q86TI2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP9	ENST00000262960.14 link	c.1855C>T	p.Arg619Cys	missense_variant	Exon 16 of 22	1	NM_139159.5	ENSP00000262960.8		Q86TI2-2

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000373

AC:

AN:

133936

Hom.:

AF XY:

0.0000396

AC XY:

AN XY:

75680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000141

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000435

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000197

AC:

AN:

1317334

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

645866

show subpopulations

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:

0.0000780

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000200

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000415

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;.;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.023

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.0096

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

.;N;.

REVEL

Benign

0.059

Sift

Benign

0.062

.;T;.

Sift4G

Benign

0.081

T;T;T

Vest4

0.48

MVP

0.11

MPC

0.96

ClinPred

0.18

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.37

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