chr16-67976166-C-T

Variant names:

• chr16-67976166-C-T
• rs377446311
• NM_001370198.1:c.1157G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001370198.1(DPEP3):​c.1157G>A​(p.Arg386His) variant causes a missense change. The variant allele was found at a frequency of 0.0000942 in 1,614,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R386C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000098 (0 hom.)
• Consequence: DPEP3 NM_001370198.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.93
• Publications: 6 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.092007935).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370198.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPEP3	NM_001370198.1	MANE Select	c.1157G>A	p.Arg386His	missense	Exon 9 of 10	NP_001357127.1	Q9H4B8
	DPEP3	NM_001129758.2		c.1154G>A	p.Arg385His	missense	Exon 9 of 10	NP_001123230.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPEP3	ENST00000268793.6	TSL:1 MANE Select	c.1157G>A	p.Arg386His	missense	Exon 9 of 10	ENSP00000268793.5	Q9H4B8
	DPEP3	ENST00000672962.1		c.1232G>A	p.Arg411His	missense	Exon 9 of 10	ENSP00000500237.1	A0A5F9ZHB4
	DPEP3	ENST00000876631.1		c.1154G>A	p.Arg385His	missense	Exon 9 of 10	ENSP00000546690.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000191 AC: 48 AN: 251462 AF XY: 0.000258

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.0000978 AC: 143 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.000128 AC XY: 93 AN XY: 727236

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000927 AC: 80 AN: 86258

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53410

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1112008

Other (OTH) AF: 0.000199 AC: 12 AN: 60392

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74492

African (AFR) AF: 0.0000962 AC: 4 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.0000604

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000247 AC: 30

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.75	T
PhyloP100		5.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.32
Sift	Benign	0.040	D
Sift4G	Uncertain	0.057	T
Vest4		0.48
MVP		0.34
MPC		0.44
ClinPred		0.26	T
GERP RS		4.8
gMVP		0.50
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs377446311; hg19: chr16-68010069; COSMIC: COSV52051539; COSMIC: COSV52051539;