16-67978361-C-G

Variant names:

• chr16-67978361-C-G
• rs1186370400
• NM_001370198.1:c.592G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001370198.1(DPEP3):​c.592G>C​(p.Gly198Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: DPEP3 NM_001370198.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.33

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPEP3	NM_001370198.1	c.592G>C	p.Gly198Arg	missense_variant	Exon 4 of 10	ENST00000268793.6	NP_001357127.1
DPEP3	NM_001129758.2	c.592G>C	p.Gly198Arg	missense_variant	Exon 4 of 10		NP_001123230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPEP3	ENST00000268793.6	c.592G>C	p.Gly198Arg	missense_variant	Exon 4 of 10	1	NM_001370198.1	ENSP00000268793.5
DPEP3	ENST00000672962.1	c.667G>C	p.Gly223Arg	missense_variant	Exon 4 of 10			ENSP00000500237.1
DPEP3	ENST00000574342.1	n.*212G>C		downstream_gene_variant		3

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

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.667G>C (p.G223R) alteration is located in exon 4 (coding exon 4) of the DPEP3 gene. This alteration results from a G to C substitution at nucleotide position 667, causing the glycine (G) at amino acid position 223 to be replaced by an arginine (R). 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	0.77
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	26
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.12	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.95
MVP		0.50
MPC		0.73
ClinPred		1.0	D
GERP RS		4.7
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1186370400; hg19: chr16-68012264;