NM_013379.3:c.1276C>T

Variant names:

• chr9-137110947-G-A
• rs149094336
• NM_013379.3:c.1276C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013379.3(DPP7):​c.1276C>T​(p.Arg426Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000419 in 1,612,804 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. R426Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: DPP7 NM_013379.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06128779).

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.1276C>T	p.Arg426Trp	missense	Exon 12 of 13	NP_037511.2	Q9UHL4
	DPP7	NM_001438108.1		c.1342C>T	p.Arg448Trp	missense	Exon 11 of 12	NP_001425037.1
	DPP7	NM_001438109.1		c.1274C>T	p.Ser425Leu	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.1276C>T	p.Arg426Trp	missense	Exon 12 of 13	ENSP00000360635.2	Q9UHL4
	DPP7	ENST00000894946.1		c.1414C>T	p.Arg472Trp	missense	Exon 12 of 13	ENSP00000565005.1
	DPP7	ENST00000894945.1		c.1363C>T	p.Arg455Trp	missense	Exon 12 of 13	ENSP00000565004.1

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000193 AC: 48 AN: 249210 AF XY: 0.000178

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000231

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000412 AC: 602 AN: 1460616 Hom.: 0 Cov.: 31 AF XY: 0.000407 AC XY: 296 AN XY: 726624

African (AFR) AF: 0.00155 AC: 52 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000485 AC: 539 AN: 1111796

Other (OTH) AF: 0.000133 AC: 8 AN: 60360

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.000471 AC XY: 35 AN XY: 74338

African (AFR) AF: 0.00123 AC: 51 AN: 41440

American (AMR) AF: 0.000131 AC: 2 AN: 15288

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68036

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000324 Hom.: 0

Bravo AF: 0.000465

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000206 AC: 25

EpiCase AF: 0.000218

EpiControl AF: 0.000178

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	0.19
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.061	T
MetaSVM	Uncertain	-0.094	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.23
Sift	Benign	0.035	D
Sift4G	Uncertain	0.029	D
Polyphen		0.97	D
Vest4		0.27
MVP		0.91
MPC		0.30
ClinPred		0.044	T
GERP RS		3.7
Varity_R		0.25
gMVP		0.79
Mutation Taster		=84/16	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: rs149094336; hg19: chr9-140005399; COSMIC: COSV108902405; COSMIC: COSV108902405;