16-67977735-G-C

Position:

• chr16-67977735-G-C

Variant summary

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

The NM_001370198.1(DPEP3):​c.851C>G​(p.Ala284Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPEP3 NM_001370198.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.63

Genes affected

DPEP3 (HGNC:23029): (dipeptidase 3) This gene encodes a membrane-bound glycoprotein from the family of dipeptidases involved in hydrolytic metabolism of various dipeptides, including penem and carbapenem beta-lactam antibiotics. This gene is located on chromosome 16 in a cluster with another member of this family. Alternatively spliced transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPEP3	NM_001370198.1	c.851C>G	p.Ala284Gly	missense_variant	6/10	ENST00000268793.6	NP_001357127.1
DPEP3	NM_001129758.2	c.851C>G	p.Ala284Gly	missense_variant	6/10		NP_001123230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPEP3	ENST00000268793.6	c.851C>G	p.Ala284Gly	missense_variant	6/10	1	NM_001370198.1	ENSP00000268793.5
DPEP3	ENST00000672962.1	c.926C>G	p.Ala309Gly	missense_variant	6/10			ENSP00000500237.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Sep 27, 2021

The c.926C>G (p.A309G) alteration is located in exon 6 (coding exon 6) of the DPEP3 gene. This alteration results from a C to G substitution at nucleotide position 926, causing the alanine (A) at amino acid position 309 to be replaced by a glycine (G). 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	Benign	0.20
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.66	T
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Vest4		0.73
MVP		0.62
MPC		0.67
ClinPred		1.0	D
GERP RS		3.4
gMVP		0.54

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: chr16-68011638;