NM_139159.5:c.56+521_56+524delTTTA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_139159.5(DPP9):​c.56+521_56+524delTTTA variant causes a 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. 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_139159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 1 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 Gene-Disease associations (from GenCC):

• hatipoglu immunodeficiency syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.234 AC: 8839 AN: 37814

American (AMR) AF: 0.101 AC: 1425 AN: 14156

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 340 AN: 3376

East Asian (EAS) AF: 0.0114 AC: 54 AN: 4732

South Asian (SAS) AF: 0.0526 AC: 219 AN: 4162

European-Finnish (FIN) AF: 0.0668 AC: 586 AN: 8766

Middle Eastern (MID) AF: 0.0993 AC: 28 AN: 282

European-Non Finnish (NFE) AF: 0.0865 AC: 5680 AN: 65630

Other (OTH) AF: 0.120 AC: 231 AN: 1930

Alfa AF: 0.0715 Hom.: 308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3059236; hg19: chr19-4719338;