rs12610495

chr19-4717660-A-Gchr19-4717660-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139159.5(DPP9):c.56+2191T>C variant causes a intron change. The variant allele was found at a frequency of 0.245 in 152,216 control chromosomes in the GnomAD database, including 4,985 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 0.25 (4984 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: DPP9 NM_139159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.251169E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP9	NM_139159.5	c.56+2191T>C		intron_variant		ENST00000262960.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP9	ENST00000262960.14	c.56+2191T>C		intron_variant		1	NM_139159.5	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37274 AN: 152090 Hom.: 4979 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.239

GnomAD3 exomes AF: 0.250 AC: 11 AN: 44 Hom.: 1 AF XY: 0.286 AC XY: 4 AN XY: 14

Gnomad AFR exome AF: 0.167

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.245 AC: 37295 AN: 152208 Hom.: 4984 Cov.: 33 AF XY: 0.244 AC XY: 18187 AN XY: 74438

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.238

Alfa AF: 0.271 Hom.: 7742

Bravo AF: 0.237

TwinsUK AF: 0.297 AC: 1103

ALSPAC AF: 0.297 AC: 1146

ExAC AF: 0.0933 AC: 372

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	17
Dann	Benign	0.65
DEOGEN2	Benign	0.092	T
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.00053	T
MutationTaster	Benign	3.9e-13	P
GERP RS		3.5

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

Other links and lift over

dbSNP: rs12610495; hg19: chr19-4717672;