X-129746638-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003399.6(XPNPEP2):​c.447T>G​(p.Pro149Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P149P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 20)
• Consequence: XPNPEP2 NM_003399.6 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-2.76 with no splicing effect.

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>G	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>G	p.Pro149Pro	synonymous	Exon 6 of 21	ENSP00000360147.3	O43895
	XPNPEP2	ENST00000880532.1		c.495T>G	p.Pro165Pro	synonymous	Exon 6 of 21	ENSP00000550591.1
	XPNPEP2	ENST00000880530.1		c.447T>G	p.Pro149Pro	synonymous	Exon 6 of 21	ENSP00000550589.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.59
DANN	Benign	0.52
PhyloP100		-2.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;