chr9-137110917-C-A

Variant names:

• chr9-137110917-C-A
• rs146742762
• NM_013379.3:c.1306G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013379.3(DPP7):​c.1306G>T​(p.Val436Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V436I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DPP7 NM_013379.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.28
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26931432).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013379.3. 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.1306G>T	p.Val436Phe	missense	Exon 12 of 13	NP_037511.2	Q9UHL4
	DPP7	NM_001438108.1		c.1372G>T	p.Val458Phe	missense	Exon 11 of 12	NP_001425037.1
	DPP7	NM_001438109.1		c.1304G>T	p.Arg435Leu	missense	Exon 11 of 12	NP_001425038.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP7	ENST00000371579.7	TSL:1 MANE Select	c.1306G>T	p.Val436Phe	missense	Exon 12 of 13	ENSP00000360635.2	Q9UHL4
	DPP7	ENST00000894946.1		c.1444G>T	p.Val482Phe	missense	Exon 12 of 13	ENSP00000565005.1
	DPP7	ENST00000894945.1		c.1393G>T	p.Val465Phe	missense	Exon 12 of 13	ENSP00000565004.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249870 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460810 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726754

African (AFR) AF: 0.0000598 AC: 2 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152246 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74424

African (AFR) AF: 0.000120 AC: 5 AN: 41554

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.51
DANN	Benign	0.94
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.3
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.84	P
Vest4		0.44
MutPred		0.58		Gain of sheet (P = 0.0827)
MVP		0.030
MPC		0.34
ClinPred		0.27	T
GERP RS		-9.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.47
gMVP		0.87
Mutation Taster		=60/40	polymorphism

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: rs146742762; hg19: chr9-140005369;