chrX-129739220-C-G

Variant names:

• chrX-129739220-C-G
• rs777882575
• NM_003399.6:c.7C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003399.6(XPNPEP2):​c.7C>G​(p.Arg3Gly) variant causes a missense 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: XPNPEP2 NM_003399.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05191499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPNPEP2	NM_003399.6	c.7C>G	p.Arg3Gly	missense_variant	Exon 1 of 21	ENST00000371106.4	NP_003390.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPNPEP2	ENST00000371106.4	c.7C>G	p.Arg3Gly	missense_variant	Exon 1 of 21	1	NM_003399.6	ENSP00000360147.3
XPNPEP2	ENST00000371105.7	n.247C>G		non_coding_transcript_exon_variant	Exon 1 of 6	2
XPNPEP2	ENST00000681234.1	n.272C>G		non_coding_transcript_exon_variant	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000557 AC: 1 AN: 179687 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65427

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.24
DANN	Benign	0.95
DEOGEN2	Benign	0.011	T;T
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.14
Sift	Benign	0.064	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.023	.;B
Vest4		0.12
MutPred		0.25		Loss of MoRF binding (P = 0.0768);Loss of MoRF binding (P = 0.0768);
MVP		0.29
MPC		0.067
ClinPred		0.13	T
GERP RS		-3.8
Varity_R		0.12
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs777882575; hg19: chrX-128873196;