chr19-33415217-T-C

Variant names:

• chr19-33415217-T-C
• rs4805885
• NM_000285.4:c.672-1574A>G

Variant summary

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

The NM_000285.4(PEPD):​c.672-1574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,726 control chromosomes in the GnomAD database, including 26,129 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 0.58 (26129 hom., cov: 33)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• Publications: 28 publications found

Genes affected

PEPD (HGNC:8840): (peptidase D) This gene encodes a member of the peptidase family. The protein forms a homodimer that hydrolyzes dipeptides or tripeptides with C-terminal proline or hydroxyproline residues. The enzyme serves an important role in the recycling of proline, and may be rate limiting for the production of collagen. Mutations in this gene result in prolidase deficiency, which is characterized by the excretion of large amount of di- and tri-peptides containing proline. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

PEPD Gene-Disease associations (from GenCC):

• prolidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000285.4. 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
	PEPD	NM_000285.4	MANE Select	c.672-1574A>G		intron	N/A	NP_000276.2	A0A140VJR2
	PEPD	NM_001166056.2		c.549-1574A>G		intron	N/A	NP_001159528.1	P12955-2
	PEPD	NM_001166057.2		c.480-1574A>G		intron	N/A	NP_001159529.1	P12955-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEPD	ENST00000244137.12	TSL:1 MANE Select	c.672-1574A>G		intron	N/A	ENSP00000244137.5	P12955-1
	PEPD	ENST00000651901.2		c.672-1574A>G		intron	N/A	ENSP00000498922.2	A0A494C165
	PEPD	ENST00000588328.7	TSL:3	c.672-1574A>G		intron	N/A	ENSP00000468516.4	K7ES25

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88492 AN: 151610 Hom.: 26099 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.573

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.584 AC: 88571 AN: 151726 Hom.: 26129 Cov.: 33 AF XY: 0.577 AC XY: 42789 AN XY: 74170

African (AFR) AF: 0.594 AC: 24537 AN: 41336

American (AMR) AF: 0.567 AC: 8649 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3464

East Asian (EAS) AF: 0.365 AC: 1883 AN: 5160

South Asian (SAS) AF: 0.348 AC: 1676 AN: 4816

European-Finnish (FIN) AF: 0.604 AC: 6369 AN: 10536

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41750 AN: 67848

Other (OTH) AF: 0.567 AC: 1194 AN: 2106

Alfa AF: 0.599 Hom.: 92322

Bravo AF: 0.589

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.20
PhyloP100		-0.51
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: rs4805885; hg19: chr19-33906123;