rs3747343

Variant names:

• chrX-129746638-T-C
• rs3747343
• NM_003399.6:c.447T>C
• XPNPEP2 p.Pro149Pro

Your query was ambiguous. Multiple possible variants found:

• chrX-129746638-T-C
• chrX-129746638-T-A
• chrX-129746638-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003399.6(XPNPEP2):​c.447T>C​(p.Pro149Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,205,591 control chromosomes in the GnomAD database, including 52,644 homozygotes. There are 128,535 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (10119 hom., 12653 hem., cov: 20)
  • Exomes 𝑓: 0.32 (42525 hom. 115882 hem.)
• Consequence: XPNPEP2 NM_003399.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.76
• Publications: 17 publications found

Genes affected

XPNPEP2 (HGNC:12823): (X-prolyl aminopeptidase 2) Aminopeptidase P is a hydrolase specific for N-terminal imido bonds, which are common to several collagen degradation products, neuropeptides, vasoactive peptides, and cytokines. Structurally, the enzyme is a member of the 'pita bread fold' family and occurs in mammalian tissues in both soluble and GPI-anchored membrane-bound forms. A membrane-bound and soluble form of this enzyme have been identified as products of two separate genes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-129746638-T-C is Benign according to our data. Variant chrX-129746638-T-C is described in ClinVar as Benign. ClinVar VariationId is 380656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003399.6. 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
	XPNPEP2	NM_003399.6	MANE Select	c.447T>C	p.Pro149Pro	synonymous	Exon 6 of 21	NP_003390.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPNPEP2	ENST00000371106.4	TSL:1 MANE Select	c.447T>C	p.Pro149Pro	synonymous	Exon 6 of 21	ENSP00000360147.3	O43895
	XPNPEP2	ENST00000880532.1		c.495T>C	p.Pro165Pro	synonymous	Exon 6 of 21	ENSP00000550591.1
	XPNPEP2	ENST00000880530.1		c.447T>C	p.Pro149Pro	synonymous	Exon 6 of 21	ENSP00000550589.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 47915 AN: 107644 Hom.: 10114 Cov.: 20

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.409

GnomAD2 exomes AF: 0.384 AC: 70472 AN: 183329 AF XY: 0.370

Gnomad AFR exome AF: 0.809

Gnomad AMR exome AF: 0.363

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.763

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.318 AC: 348687 AN: 1097890 Hom.: 42525 Cov.: 32 AF XY: 0.319 AC XY: 115882 AN XY: 363380

African (AFR) AF: 0.814 AC: 21488 AN: 26389

American (AMR) AF: 0.366 AC: 12884 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 4548 AN: 19385

East Asian (EAS) AF: 0.751 AC: 22680 AN: 30202

South Asian (SAS) AF: 0.431 AC: 23305 AN: 54133

European-Finnish (FIN) AF: 0.292 AC: 11816 AN: 40467

Middle Eastern (MID) AF: 0.284 AC: 1169 AN: 4117

European-Non Finnish (NFE) AF: 0.279 AC: 234876 AN: 841915

Other (OTH) AF: 0.345 AC: 15921 AN: 46086

GnomAD4 genome AF: 0.445 AC: 47973 AN: 107701 Hom.: 10119 Cov.: 20 AF XY: 0.419 AC XY: 12653 AN XY: 30219

African (AFR) AF: 0.792 AC: 23007 AN: 29058

American (AMR) AF: 0.360 AC: 3658 AN: 10168

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 646 AN: 2607

East Asian (EAS) AF: 0.768 AC: 2561 AN: 3333

South Asian (SAS) AF: 0.430 AC: 1022 AN: 2375

European-Finnish (FIN) AF: 0.269 AC: 1520 AN: 5659

Middle Eastern (MID) AF: 0.310 AC: 65 AN: 210

European-Non Finnish (NFE) AF: 0.281 AC: 14645 AN: 52144

Other (OTH) AF: 0.412 AC: 608 AN: 1476

Alfa AF: 0.356 Hom.: 39811

Bravo AF: 0.476

EpiCase AF: 0.266

EpiControl AF: 0.276

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.53
DANN	Benign	0.51
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3747343;

hg19: chrX-128880614;

COSMIC: COSV64367834;