NM_000285.4:c.671+1947A>G

Variant names:

• chr19-33461048-T-C
• rs10422643
• NM_000285.4:c.671+1947A>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.671+1947A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,010 control chromosomes in the GnomAD database, including 18,871 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 0.49 (18871 hom., cov: 32)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 4 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEPD	NM_000285.4	c.671+1947A>G		intron_variant	Intron 9 of 14	ENST00000244137.12	NP_000276.2
PEPD	NM_001166056.2	c.548+16998A>G		intron_variant	Intron 7 of 12		NP_001159528.1
PEPD	NM_001166057.2	c.479+1947A>G		intron_variant	Intron 7 of 12		NP_001159529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEPD	ENST00000244137.12	c.671+1947A>G		intron_variant	Intron 9 of 14	1	NM_000285.4	ENSP00000244137.5

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74673 AN: 151892 Hom.: 18850 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.492 AC: 74746 AN: 152010 Hom.: 18871 Cov.: 32 AF XY: 0.486 AC XY: 36141 AN XY: 74298

African (AFR) AF: 0.595 AC: 24666 AN: 41462

American (AMR) AF: 0.486 AC: 7429 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1130 AN: 5172

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4822

European-Finnish (FIN) AF: 0.477 AC: 5035 AN: 10550

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32013 AN: 67954

Other (OTH) AF: 0.472 AC: 996 AN: 2108

Alfa AF: 0.489 Hom.: 3193

Bravo AF: 0.504

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.047
DANN	Benign	0.29
PhyloP100		-1.6
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: rs10422643; hg19: chr19-33951954;