16-67977338-A-T

Position:

• chr16-67977338-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001370198.1(DPEP3):​c.950T>A​(p.Ile317Asn) variant causes a missense change involving the alteration of a non-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: 2.94

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPEP3	NM_001370198.1	c.950T>A	p.Ile317Asn	missense_variant	7/10	ENST00000268793.6	NP_001357127.1
DPEP3	NM_001129758.2	c.947T>A	p.Ile316Asn	missense_variant	7/10		NP_001123230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPEP3	ENST00000268793.6	c.950T>A	p.Ile317Asn	missense_variant	7/10	1	NM_001370198.1	ENSP00000268793.5
DPEP3	ENST00000672962.1	c.1025T>A	p.Ile342Asn	missense_variant	7/10			ENSP00000500237.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 12, 2021

The c.1025T>A (p.I342N) alteration is located in exon 7 (coding exon 7) of the DPEP3 gene. This alteration results from a T to A substitution at nucleotide position 1025, causing the isoleucine (I) at amino acid position 342 to be replaced by an asparagine (N). 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	Uncertain	0.55
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.55	T
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.91
MVP		0.48
MPC		0.89
ClinPred		0.99	D
GERP RS		5.2
gMVP		0.87

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: chr16-68011241;