NM_013379.3:c.1435G>C

Variant names:

• chr9-137110692-C-G
• rs1366795757
• NM_013379.3:c.1435G>C

Variant summary

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

The NM_013379.3(DPP7):​c.1435G>C​(p.Glu479Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DPP7 NM_013379.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.45
• Publications: 0 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 (MetaRNN=0.06378248).

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.1435G>C	p.Glu479Gln	missense	Exon 13 of 13	NP_037511.2	Q9UHL4
	DPP7	NM_001438108.1		c.1501G>C	p.Glu501Gln	missense	Exon 12 of 12	NP_001425037.1
	DPP7	NM_001438109.1		c.*56G>C		3_prime_UTR	Exon 12 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.1435G>C	p.Glu479Gln	missense	Exon 13 of 13	ENSP00000360635.2	Q9UHL4
	DPP7	ENST00000894946.1		c.1573G>C	p.Glu525Gln	missense	Exon 13 of 13	ENSP00000565005.1
	DPP7	ENST00000894945.1		c.1522G>C	p.Glu508Gln	missense	Exon 13 of 13	ENSP00000565004.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457044 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724996

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44712

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4288

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111928

Other (OTH) AF: 0.00 AC: 0 AN: 60194

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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	0.080
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.63
DANN	Benign	0.73
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.0050
Sift	Benign	0.19	T
Sift4G	Benign	0.27	T
Polyphen		0.0060	B
Vest4		0.17
MutPred		0.25		Loss of ubiquitination at K474 (P = 0.0531)
MVP		0.072
MPC		0.075
ClinPred		0.085	T
GERP RS		-8.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.36
Mutation Taster		=94/6	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: rs1366795757; hg19: chr9-140005144;