chr9-137110894-G-A

Variant names:

• chr9-137110894-G-A
• rs750189450
• NM_013379.3:c.1329C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001438109.1(DPP7):​c.1327C>T​(p.Pro443Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P443A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DPP7 NM_001438109.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 1 publications found

Genes affected

DPP7 (HGNC:14892): (dipeptidyl peptidase 7) The protein encoded by this gene is a post-proline cleaving aminopeptidase expressed in quiescent lymphocytes. The resting lymphocytes are maintained through suppression of apoptosis, a state which is disrupted by inhibition of this novel serine protease. The enzyme has strong sequence homology with prolylcarboxypeptidase and is active at both acidic and neutral pH. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438109.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP7	NM_013379.3	MANE Select	c.1329C>T	p.His443His	synonymous	Exon 12 of 13	NP_037511.2	Q9UHL4
	DPP7	NM_001438109.1		c.1327C>T	p.Pro443Ser	missense	Exon 11 of 12	NP_001425038.1
	DPP7	NM_001438110.1		c.1261C>T	p.Pro421Ser	missense	Exon 12 of 13	NP_001425039.1	A0ABB0MVF0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP7	ENST00000371579.7	TSL:1 MANE Select	c.1329C>T	p.His443His	synonymous	Exon 12 of 13	ENSP00000360635.2	Q9UHL4
	DPP7	ENST00000718334.1		c.1261C>T	p.Pro421Ser	missense	Exon 12 of 13	ENSP00000520771.1	A0ABB0MVF0
	DPP7	ENST00000894946.1		c.1467C>T	p.His489His	synonymous	Exon 12 of 13	ENSP00000565005.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460392 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726508

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52216

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111852

Other (OTH) AF: 0.0000166 AC: 1 AN: 60364

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.036
DANN	Benign	0.93
PhyloP100		-0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs750189450; hg19: chr9-140005346;