chr11-66482426-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_130443.4(DPP3):​c.226C>T​(p.Arg76Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,608,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R76H) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: DPP3 NM_130443.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30813417).

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.226C>T	p.Arg76Cys	missense	Exon 2 of 18	NP_569710.2	Q9NY33-1
	DPP3	NM_005700.5		c.226C>T	p.Arg76Cys	missense	Exon 2 of 18	NP_005691.2
	DPP3	NM_001256670.2		c.226C>T	p.Arg76Cys	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.226C>T	p.Arg76Cys	missense	Exon 2 of 18	ENSP00000432782.2	Q9NY33-1
	DPP3	ENST00000532677.5	TSL:1	c.283C>T	p.Arg95Cys	missense	Exon 2 of 18	ENSP00000435284.1	G3V1D3
	DPP3	ENST00000883964.1		c.226C>T	p.Arg76Cys	missense	Exon 2 of 18	ENSP00000554023.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152258 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000445 AC: 11 AN: 247130 AF XY: 0.0000597

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000970

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000189 AC: 276 AN: 1456626 Hom.: 0 Cov.: 31 AF XY: 0.000195 AC XY: 141 AN XY: 724890

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000242 AC: 269 AN: 1111984

Other (OTH) AF: 0.0000828 AC: 5 AN: 60352

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74390

African (AFR) AF: 0.0000482 AC: 2 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000983 Hom.: 0

Bravo AF: 0.0000756

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.3
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.23
MVP		0.49
ClinPred		0.62	D
GERP RS		3.8
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.48
gMVP		0.31
Mutation Taster		=86/14	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: rs199654699; hg19: chr11-66249897;