19-4682811-C-A

Variant names:

• chr19-4682811-C-A
• rs761296885
• NM_139159.5:c.2359G>T

Variant summary

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

The NM_139159.5(DPP9):​c.2359G>T​(p.Val787Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,520 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V787I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DPP9 NM_139159.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2359G>T	p.Val787Phe	missense	Exon 20 of 22	NP_631898.3
	DPP9	NM_001384611.1		c.2359G>T	p.Val787Phe	missense	Exon 19 of 21	NP_001371540.1	Q86TI2-2
	DPP9	NM_001384612.1		c.2359G>T	p.Val787Phe	missense	Exon 21 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.2359G>T	p.Val787Phe	missense	Exon 20 of 22	ENSP00000262960.8	Q86TI2-2
	DPP9	ENST00000600621.6	TSL:4	c.2359G>T	p.Val787Phe	missense	Exon 20 of 22	ENSP00000472549.2	Q86TI2-2
	DPP9	ENST00000601130.6	TSL:4	c.2359G>T	p.Val787Phe	missense	Exon 21 of 23	ENSP00000471629.2	Q86TI2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440520 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 714682

African (AFR) AF: 0.00 AC: 0 AN: 33034

American (AMR) AF: 0.00 AC: 0 AN: 41124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.00 AC: 0 AN: 38612

South Asian (SAS) AF: 0.00 AC: 0 AN: 82966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102250

Other (OTH) AF: 0.00 AC: 0 AN: 59662

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		2.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Benign	0.11	T
Sift4G	Benign	0.71	T
Vest4		0.80
MutPred		0.61		Loss of catalytic residue at T786 (P = 0.2911)
MVP		0.40
MPC		2.4
ClinPred		0.86	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.91
Mutation Taster		=55/45	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: rs761296885; hg19: chr19-4682823;