rs760300794

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-89630426-T-A
• chr16-89630426-T-C
• chr16-89630426-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001389466.1(DPEP1):​c.16T>A​(p.Trp6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. W6G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 27)
• Consequence: DPEP1 NM_001389466.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPEP1	NM_001389466.1	c.16T>A	p.Trp6Arg	missense_variant	Exon 2 of 11	ENST00000690203.1	NP_001376395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPEP1	ENST00000690203.1	c.16T>A	p.Trp6Arg	missense_variant	Exon 2 of 11		NM_001389466.1	ENSP00000508584.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 27

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.036	T;T;T;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.52	T;T;T;.;.
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	.;M;.;M;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.61	N;N;N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0060	D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		0.20	.;B;.;B;B
Vest4		0.70, 0.70
MutPred		0.69		Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);
MVP		0.048
MPC		0.071
ClinPred		0.93	D
GERP RS		3.8
Varity_R		0.23
gMVP		0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs760300794; hg19: chr16-89696834;