NM_001389466.1:c.613C>A

Variant names:

• chr16-89637225-C-A
• rs376403325
• NM_001389466.1:c.613C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001389466.1(DPEP1):​c.613C>A​(p.Arg205Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R205C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPEP1 NM_001389466.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74
• Publications: 1 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

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.613C>A	p.Arg205Ser	missense	Exon 7 of 11	NP_001376395.1	P16444
	DPEP1	NM_001128141.3		c.613C>A	p.Arg205Ser	missense	Exon 7 of 11	NP_001121613.1	A0A140VJI3
	DPEP1	NM_001389467.1		c.613C>A	p.Arg205Ser	missense	Exon 7 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.613C>A	p.Arg205Ser	missense	Exon 7 of 11	ENSP00000508584.1	P16444
	DPEP1	ENST00000261615.5	TSL:1	c.613C>A	p.Arg205Ser	missense	Exon 6 of 10	ENSP00000261615.4	P16444
	DPEP1	ENST00000393092.7	TSL:1	c.613C>A	p.Arg205Ser	missense	Exon 7 of 11	ENSP00000376807.3	P16444

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.092	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.84		Loss of MoRF binding (P = 0.0583)
MVP		0.22
MPC		0.15
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.99
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs376403325; hg19: chr16-89703633;