19-4719326-TTAAATAAATAAATAAATAAATAAA-TTAAATAAATAAATAAATAAA

Variant names:

• chr19-4719326-TTAAA-T
• rs3059236
• NM_139159.5:c.56+521_56+524delTTTA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001384624.1(DPP9):​c.-153-6_-153-3delTTTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 141,740 control chromosomes in the GnomAD database, including 1,399 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1399 hom., cov: 0)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: DPP9 NM_001384624.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP9	NM_139159.5	c.56+521_56+524delTTTA		intron_variant	Intron 3 of 21	ENST00000262960.14	NP_631898.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP9	ENST00000262960.14	c.56+521_56+524delTTTA		intron_variant	Intron 3 of 21	1	NM_139159.5	ENSP00000262960.8

Frequencies

GnomAD3 genomes AF: 0.124 AC: 17528 AN: 141630 Hom.: 1389 Cov.: 0

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.0529

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.124 AC: 17554 AN: 141728 Hom.: 1399 Cov.: 0 AF XY: 0.121 AC XY: 8306 AN XY: 68392

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.0865

Gnomad4 OTH AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3059236; hg19: chr19-4719338;