rs199654699

Variant names:

• chr11-66482426-C-G
• rs199654699
• NM_130443.4:c.226C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-66482426-C-G
• chr11-66482426-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130443.4(DPP3):​c.226C>G​(p.Arg76Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R76H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DPP3 NM_130443.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

Genes affected

DPP3 (HGNC:3008): (dipeptidyl peptidase 3) This gene encodes a protein that is a member of the M49 family of metallopeptidases. This cytoplasmic protein binds a single zinc ion with its zinc-binding motif (HELLGH) and has post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Increased activity of this protein is associated with endometrial and ovarian cancers. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2447519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP3	NM_130443.4	c.226C>G	p.Arg76Gly	missense_variant	Exon 2 of 18	ENST00000531863.6	NP_569710.2
DPP3	NM_005700.5	c.226C>G	p.Arg76Gly	missense_variant	Exon 2 of 18		NP_005691.2
DPP3	NM_001256670.2	c.226C>G	p.Arg76Gly	missense_variant	Exon 2 of 17		NP_001243599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP3	ENST00000531863.6	c.226C>G	p.Arg76Gly	missense_variant	Exon 2 of 18	1	NM_130443.4	ENSP00000432782.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456626 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T;T;T;T;.;T;.
Eigen	Benign	-0.040
Eigen_PC	Benign	0.083
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.77	T;T;T;T;T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.24	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	.;.;N;.;N;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D;D;D;D;D;D;D
Sift4G	Uncertain	0.032	D;D;D;T;T;T;T
Polyphen		0.41, 0.0010	.;B;B;.;.;.;.
Vest4		0.14
MutPred		0.44		.;Loss of helix (P = 0.0304);.;.;.;.;.;
MVP		0.37
ClinPred		0.68	D
GERP RS		3.8
Varity_R		0.49
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs199654699; hg19: chr11-66249897;