NM_139159.5:c.56+517_56+524dupTTTATTTA

Variant names:

• chr19-4719326-T-TTAAATAAA
• rs3059236
• NM_139159.5:c.56+517_56+524dupTTTATTTA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_139159.5(DPP9):​c.56+517_56+524dupTTTATTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (24 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPP9 NM_139159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.964
• 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.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0154 (2192/141892) while in subpopulation NFE AF = 0.0178 (1172/65662). AF 95% confidence interval is 0.017. There are 24 homozygotes in GnomAd4. There are 1101 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP9	NM_139159.5	c.56+517_56+524dupTTTATTTA		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+524_56+525insTTTATTTA		intron_variant	Intron 3 of 21	1	NM_139159.5	ENSP00000262960.8

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2194 AN: 141796 Hom.: 24 Cov.: 0

Gnomad AFR AF: 0.00984

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0392

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0147

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

African (AFR) AF: 0.00 AC: 0 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: 0.0154 AC: 2192 AN: 141892 Hom.: 24 Cov.: 0 AF XY: 0.0161 AC XY: 1101 AN XY: 68476

African (AFR) AF: 0.00984 AC: 373 AN: 37924

American (AMR) AF: 0.0176 AC: 249 AN: 14164

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 46 AN: 3376

East Asian (EAS) AF: 0.0146 AC: 69 AN: 4732

South Asian (SAS) AF: 0.0166 AC: 69 AN: 4166

European-Finnish (FIN) AF: 0.0198 AC: 174 AN: 8774

Middle Eastern (MID) AF: 0.0390 AC: 11 AN: 282

European-Non Finnish (NFE) AF: 0.0178 AC: 1172 AN: 65662

Other (OTH) AF: 0.0150 AC: 29 AN: 1930

Alfa AF: 0.0112 Hom.: 308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3059236; hg19: chr19-4719338;