rs255049

Variant names:

• chr16-67979568-T-C
• rs255049
• NM_001370198.1:c.414+71A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370198.1(DPEP3):​c.414+71A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,592,654 control chromosomes in the GnomAD database, including 48,301 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (11878 hom., cov: 32)
  • Exomes 𝑓: 0.21 (36423 hom.)
• Consequence: DPEP3 NM_001370198.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 78 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPEP3	NM_001370198.1	c.414+71A>G		intron_variant	Intron 2 of 9	ENST00000268793.6	NP_001357127.1
DPEP3	NM_001129758.2	c.414+71A>G		intron_variant	Intron 2 of 9		NP_001123230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPEP3	ENST00000268793.6	c.414+71A>G		intron_variant	Intron 2 of 9	1	NM_001370198.1	ENSP00000268793.5
DPEP3	ENST00000672962.1	c.489+71A>G		intron_variant	Intron 2 of 9			ENSP00000500237.1
DPEP3	ENST00000574342.1	n.415+526A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50634 AN: 151984 Hom.: 11848 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.209 AC: 300490 AN: 1440552 Hom.: 36423 AF XY: 0.209 AC XY: 149300 AN XY: 714796

African (AFR) AF: 0.693 AC: 22945 AN: 33120

American (AMR) AF: 0.224 AC: 9732 AN: 43466

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 5948 AN: 25002

East Asian (EAS) AF: 0.137 AC: 5376 AN: 39384

South Asian (SAS) AF: 0.264 AC: 22112 AN: 83834

European-Finnish (FIN) AF: 0.216 AC: 11032 AN: 51190

Middle Eastern (MID) AF: 0.263 AC: 1104 AN: 4200

European-Non Finnish (NFE) AF: 0.190 AC: 208801 AN: 1101004

Other (OTH) AF: 0.226 AC: 13440 AN: 59352

GnomAD4 genome AF: 0.333 AC: 50722 AN: 152102 Hom.: 11878 Cov.: 32 AF XY: 0.331 AC XY: 24627 AN XY: 74336

African (AFR) AF: 0.671 AC: 27808 AN: 41468

American (AMR) AF: 0.252 AC: 3845 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 810 AN: 3468

East Asian (EAS) AF: 0.116 AC: 602 AN: 5168

South Asian (SAS) AF: 0.255 AC: 1227 AN: 4816

European-Finnish (FIN) AF: 0.221 AC: 2344 AN: 10590

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13082 AN: 67996

Other (OTH) AF: 0.308 AC: 652 AN: 2114

Alfa AF: 0.238 Hom.: 19936

Bravo AF: 0.347

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.9
DANN	Benign	0.74
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs255049; hg19: chr16-68013471; COSMIC: COSV52050274;