16-67975917-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370198.1(DPEP3):​c.1315G>A​(p.Val439Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

DPEP3
NM_001370198.1 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.345
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0096654).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DPEP3NM_001370198.1 linkc.1315G>A p.Val439Met missense_variant Exon 10 of 10 ENST00000268793.6 NP_001357127.1
DPEP3NM_001129758.2 linkc.1312G>A p.Val438Met missense_variant Exon 10 of 10 NP_001123230.2 Q9H4B8A0A140VK16

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DPEP3ENST00000268793.6 linkc.1315G>A p.Val439Met missense_variant Exon 10 of 10 1 NM_001370198.1 ENSP00000268793.5 Q9H4B8
DPEP3ENST00000672962.1 linkc.1390G>A p.Val464Met missense_variant Exon 10 of 10 ENSP00000500237.1 A0A5F9ZHB4

Frequencies

GnomAD3 genomes
AF:
0.000309
AC:
47
AN:
152156
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000104
AC:
26
AN:
250650
Hom.:
0
AF XY:
0.0000811
AC XY:
11
AN XY:
135568
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000442
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000985
AC:
144
AN:
1461638
Hom.:
0
Cov.:
31
AF XY:
0.0000963
AC XY:
70
AN XY:
727086
show subpopulations
Gnomad4 AFR exome
AF:
0.000956
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000899
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000315
AC:
48
AN:
152274
Hom.:
0
Cov.:
33
AF XY:
0.000255
AC XY:
19
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00103
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000257
Hom.:
0
Bravo
AF:
0.000385
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.000132
AC:
16
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 02, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1390G>A (p.V464M) alteration is located in exon 10 (coding exon 10) of the DPEP3 gene. This alteration results from a G to A substitution at nucleotide position 1390, causing the valine (V) at amino acid position 464 to be replaced by a methionine (M). 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
0.083
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
5.7
DANN
Benign
0.63
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.041
N
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.0097
T
MetaSVM
Benign
-0.98
T
PrimateAI
Benign
0.23
T
PROVEAN
Benign
0.20
N
REVEL
Benign
0.021
Sift
Benign
0.10
T
Sift4G
Benign
0.14
T
Vest4
0.17
MVP
0.061
MPC
0.16
ClinPred
0.0032
T
GERP RS
-1.7
gMVP
0.060

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199987960; hg19: chr16-68009820; API