rs201658473

Variant names:

• chr11-66482270-C-G
• rs201658473
• NM_130443.4:c.70C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-66482270-C-G
• chr11-66482270-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130443.4(DPP3):​c.70C>G​(p.Arg24Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. R24C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPP3 NM_130443.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23478052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130443.4. 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
	DPP3	NM_130443.4	MANE Select	c.70C>G	p.Arg24Gly	missense	Exon 2 of 18	NP_569710.2	Q9NY33-1
	DPP3	NM_005700.5		c.70C>G	p.Arg24Gly	missense	Exon 2 of 18	NP_005691.2
	DPP3	NM_001256670.2		c.70C>G	p.Arg24Gly	missense	Exon 2 of 17	NP_001243599.1	Q9NY33-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP3	ENST00000531863.6	TSL:1 MANE Select	c.70C>G	p.Arg24Gly	missense	Exon 2 of 18	ENSP00000432782.2	Q9NY33-1
	DPP3	ENST00000532677.5	TSL:1	c.127C>G	p.Arg43Gly	missense	Exon 2 of 18	ENSP00000435284.1	G3V1D3
	DPP3	ENST00000883964.1		c.70C>G	p.Arg24Gly	missense	Exon 2 of 18	ENSP00000554023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.094
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.0
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.21	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.32
MutPred		0.34		Gain of relative solvent accessibility (P = 0.0522)
MVP		0.59
ClinPred		0.63	D
GERP RS		4.9
PromoterAI		0.0014	Neutral
Varity_R		0.46
gMVP		0.30
Mutation Taster		=69/31	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: rs201658473; hg19: chr11-66249741;