19-4688787-G-C

Variant names:

• chr19-4688787-G-C
• rs369048539
• NM_139159.5:c.1855C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139159.5(DPP9):​c.1855C>G​(p.Arg619Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 1,317,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R619S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: DPP9 NM_139159.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 0 publications found

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-AS1 (HGNC:50706): (DPP9 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16874325).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP9	NM_139159.5	MANE Select	c.1855C>G	p.Arg619Gly	missense	Exon 16 of 22	NP_631898.3
	DPP9	NM_001384611.1		c.1855C>G	p.Arg619Gly	missense	Exon 15 of 21	NP_001371540.1	Q86TI2-2
	DPP9	NM_001384612.1		c.1855C>G	p.Arg619Gly	missense	Exon 17 of 23	NP_001371541.1	Q86TI2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP9	ENST00000262960.14	TSL:1 MANE Select	c.1855C>G	p.Arg619Gly	missense	Exon 16 of 22	ENSP00000262960.8	Q86TI2-2
	DPP9	ENST00000600621.6	TSL:4	c.1855C>G	p.Arg619Gly	missense	Exon 16 of 22	ENSP00000472549.2	Q86TI2-2
	DPP9	ENST00000601130.6	TSL:4	c.1855C>G	p.Arg619Gly	missense	Exon 17 of 23	ENSP00000471629.2	Q86TI2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000228 AC: 3 AN: 1317336 Hom.: 0 Cov.: 30 AF XY: 0.00000155 AC XY: 1 AN XY: 645868

African (AFR) AF: 0.00 AC: 0 AN: 25956

American (AMR) AF: 0.00 AC: 0 AN: 19000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20880

East Asian (EAS) AF: 0.00 AC: 0 AN: 31272

South Asian (SAS) AF: 0.00 AC: 0 AN: 64070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5280

European-Non Finnish (NFE) AF: 0.00000286 AC: 3 AN: 1048280

Other (OTH) AF: 0.00 AC: 0 AN: 54236

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.0
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.027
Sift	Benign	0.31	T
Sift4G	Benign	0.41	T
Vest4		0.37
MutPred		0.49		Gain of catalytic residue at F620 (P = 0.0557)
MVP		0.13
MPC		0.52
ClinPred		0.32	T
GERP RS		3.8
PromoterAI		-0.00090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.39
gMVP		0.33
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs369048539; hg19: chr19-4688799;