chr19-4719326-T-TTAAA

Variant names:

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

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+524dupTTTA 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 0.33 (8070 hom., cov: 0)
  • Exomes 𝑓: 0.33 (1 hom.)
• 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.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 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+524dupTTTA		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+525insTTTA		intron_variant	Intron 3 of 21	1	NM_139159.5	ENSP00000262960.8

Frequencies

GnomAD3 genomes AF: 0.333 AC: 47070 AN: 141436 Hom.: 8058 Cov.: 0

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.431

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.333 AC: 4 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.125 AC XY: 1 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: 0.400 AC: 4 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.333 AC: 47098 AN: 141530 Hom.: 8070 Cov.: 0 AF XY: 0.336 AC XY: 22928 AN XY: 68314

African (AFR) AF: 0.315 AC: 11924 AN: 37820

American (AMR) AF: 0.309 AC: 4366 AN: 14120

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1737 AN: 3366

East Asian (EAS) AF: 0.419 AC: 1981 AN: 4730

South Asian (SAS) AF: 0.522 AC: 2158 AN: 4138

European-Finnish (FIN) AF: 0.325 AC: 2833 AN: 8730

Middle Eastern (MID) AF: 0.440 AC: 124 AN: 282

European-Non Finnish (NFE) AF: 0.322 AC: 21075 AN: 65540

Other (OTH) AF: 0.360 AC: 691 AN: 1922

Alfa AF: 0.309 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 (auto)

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;