16-67978376-T-G

Position:

• chr16-67978376-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370198.1(DPEP3):​c.577A>C​(p.Ile193Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: DPEP3 NM_001370198.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31944284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPEP3	NM_001370198.1	c.577A>C	p.Ile193Leu	missense_variant	4/10	ENST00000268793.6	NP_001357127.1
DPEP3	NM_001129758.2	c.577A>C	p.Ile193Leu	missense_variant	4/10		NP_001123230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPEP3	ENST00000268793.6	c.577A>C	p.Ile193Leu	missense_variant	4/10	1	NM_001370198.1	ENSP00000268793.5
DPEP3	ENST00000672962.1	c.652A>C	p.Ile218Leu	missense_variant	4/10			ENSP00000500237.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461734 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.000109

EpiControl AF: 0.00

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

Aug 20, 2024

The c.652A>C (p.I218L) alteration is located in exon 4 (coding exon 4) of the DPEP3 gene. This alteration results from a A to C substitution at nucleotide position 652, causing the isoleucine (I) at amino acid position 218 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.98
Eigen	Benign	0.046
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Benign	0.17	T
Sift4G	Benign	0.071	T
Vest4		0.52
MVP		0.10
MPC		0.59
ClinPred		0.94	D
GERP RS		4.7
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs755916313; hg19: chr16-68012279;