chr16-89636626-C-T

Variant names:

• chr16-89636626-C-T
• rs78315344
• NM_001389466.1:c.464C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001389466.1(DPEP1):​c.464C>T​(p.Ala155Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. A155E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DPEP1 NM_001389466.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120817244).

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.464C>T	p.Ala155Val	missense	Exon 5 of 11	NP_001376395.1	P16444
	DPEP1	NM_001128141.3		c.464C>T	p.Ala155Val	missense	Exon 5 of 11	NP_001121613.1	A0A140VJI3
	DPEP1	NM_001389467.1		c.464C>T	p.Ala155Val	missense	Exon 5 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.464C>T	p.Ala155Val	missense	Exon 5 of 11	ENSP00000508584.1	P16444
	DPEP1	ENST00000261615.5	TSL:1	c.464C>T	p.Ala155Val	missense	Exon 4 of 10	ENSP00000261615.4	P16444
	DPEP1	ENST00000393092.7	TSL:1	c.464C>T	p.Ala155Val	missense	Exon 5 of 11	ENSP00000376807.3	P16444

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248834 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: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460320 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726476

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

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

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111954

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15310

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.44
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.090
Sift	Benign	0.062	T
Sift4G	Benign	0.23	T
Polyphen		0.039	B
Vest4		0.28
MutPred		0.42		Gain of helix (P = 0.2059)
MVP		0.048
MPC		0.019
ClinPred		0.56	D
GERP RS		5.1
Varity_R		0.31
gMVP		0.49
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs78315344; hg19: chr16-89703034;