NM_001389466.1:c.16T>G

Variant names:

• chr16-89630426-T-G
• rs760300794
• NM_001389466.1:c.16T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001389466.1(DPEP1):​c.16T>G​(p.Trp6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,610,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: DPEP1 NM_001389466.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67
• Publications: 0 publications found

Genes affected

DPEP1 (HGNC:3002): (dipeptidase 1) The protein encoded by this gene is a kidney membrane enzyme involved in the metabolism of glutathione and other similar proteins by dipeptide hydrolysis. The encoded protein is known to regulate leukotriene activity by catalyzing the conversion of leukotriene D4 to leukotriene E4. This protein uses zinc as a cofactor and acts as a disulfide-linked homodimer. [provided by RefSeq, Dec 2020]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389466.1. 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
	DPEP1	NM_001389466.1	MANE Select	c.16T>G	p.Trp6Gly	missense	Exon 2 of 11	NP_001376395.1	P16444
	DPEP1	NM_001128141.3		c.16T>G	p.Trp6Gly	missense	Exon 2 of 11	NP_001121613.1	A0A140VJI3
	DPEP1	NM_001389467.1		c.16T>G	p.Trp6Gly	missense	Exon 2 of 11	NP_001376396.1	P16444

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPEP1	ENST00000690203.1	MANE Select	c.16T>G	p.Trp6Gly	missense	Exon 2 of 11	ENSP00000508584.1	P16444
	DPEP1	ENST00000261615.5	TSL:1	c.16T>G	p.Trp6Gly	missense	Exon 1 of 10	ENSP00000261615.4	P16444
	DPEP1	ENST00000393092.7	TSL:1	c.16T>G	p.Trp6Gly	missense	Exon 2 of 11	ENSP00000376807.3	P16444

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 150918 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000590

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249380 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459264 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725934

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 86076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110704

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 150918 Hom.: 0 Cov.: 27 AF XY: 0.0000136 AC XY: 1 AN XY: 73610

African (AFR) AF: 0.00 AC: 0 AN: 40992

American (AMR) AF: 0.00 AC: 0 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000590 AC: 4 AN: 67758

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

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	0.14
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.7
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.21
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.17	B
Vest4		0.60
MutPred		0.74		Gain of disorder (P = 0.002)
MVP		0.040
MPC		0.081
ClinPred		0.60	D
GERP RS		3.8
PromoterAI		-0.042	Neutral
Varity_R		0.27
gMVP		0.63

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: rs760300794; hg19: chr16-89696834;