11-66485225-C-A

Position:

• chr11-66485225-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_130443.4(DPP3):​c.323C>A​(p.Ser108Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPP3 NM_130443.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP3	NM_130443.4	c.323C>A	p.Ser108Tyr	missense_variant	3/18	ENST00000531863.6	NP_569710.2
DPP3	NM_005700.5	c.323C>A	p.Ser108Tyr	missense_variant	3/18		NP_005691.2
DPP3	NM_001256670.2	c.271-1315C>A		intron_variant			NP_001243599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP3	ENST00000531863.6	c.323C>A	p.Ser108Tyr	missense_variant	3/18	1	NM_130443.4	ENSP00000432782	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.323C>A (p.S108Y) alteration is located in exon 3 (coding exon 2) of the DPP3 gene. This alteration results from a C to A substitution at nucleotide position 323, causing the serine (S) at amino acid position 108 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;D;T;.;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D;D
MetaSVM	Uncertain	0.065	D
MutationAssessor	Pathogenic	3.4	.;.;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.6	D;D;D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0060	D;D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D;D
Polyphen		1.0	.;.;D;.;.;.
Vest4		0.94
MutPred		0.50		.;.;Loss of disorder (P = 0.0399);.;.;Loss of disorder (P = 0.0399);
MVP		0.88
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.74
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-66252696;