NM_000285.4:c.548+4771A>G

Variant names:

• chr19-33473275-T-C
• rs11880064
• NM_000285.4:c.548+4771A>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.548+4771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,924 control chromosomes in the GnomAD database, including 14,172 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 0.42 (14172 hom., cov: 31)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 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.548+4771A>G		intron	N/A	NP_000276.2	A0A140VJR2
	PEPD	NM_001166056.2		c.548+4771A>G		intron	N/A	NP_001159528.1	P12955-2
	PEPD	NM_001166057.2		c.356+4771A>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.548+4771A>G		intron	N/A	ENSP00000244137.5	P12955-1
	PEPD	ENST00000651901.2		c.548+4771A>G		intron	N/A	ENSP00000498922.2	A0A494C165
	PEPD	ENST00000588328.7	TSL:3	c.548+4771A>G		intron	N/A	ENSP00000468516.4	K7ES25

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63649 AN: 151806 Hom.: 14154 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.419 AC: 63718 AN: 151924 Hom.: 14172 Cov.: 31 AF XY: 0.417 AC XY: 30943 AN XY: 74286

African (AFR) AF: 0.573 AC: 23724 AN: 41416

American (AMR) AF: 0.432 AC: 6594 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3466

East Asian (EAS) AF: 0.216 AC: 1114 AN: 5146

South Asian (SAS) AF: 0.275 AC: 1319 AN: 4802

European-Finnish (FIN) AF: 0.357 AC: 3775 AN: 10570

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24600 AN: 67928

Other (OTH) AF: 0.403 AC: 852 AN: 2114

Alfa AF: 0.377 Hom.: 6005

Bravo AF: 0.437

Asia WGS AF: 0.291 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.23
PhyloP100		-1.8
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: rs11880064; hg19: chr19-33964181;