rs777882575

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-129739220-C-A
• chrX-129739220-C-G
• chrX-129739220-C-T

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.7C>A​(p.Arg3Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,095,972 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: XPNPEP2 NM_003399.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 0 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=-0.52).
• BP7: Synonymous conserved (PhyloP=-2.47 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.7C>A	p.Arg3Arg	synonymous	Exon 1 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.7C>A	p.Arg3Arg	synonymous	Exon 1 of 21	ENSP00000360147.3	O43895
	XPNPEP2	ENST00000880532.1		c.7C>A	p.Arg3Arg	synonymous	Exon 1 of 21	ENSP00000550591.1
	XPNPEP2	ENST00000880530.1		c.7C>A	p.Arg3Arg	synonymous	Exon 1 of 21	ENSP00000550589.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1095972 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 362210

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26387

American (AMR) AF: 0.00 AC: 0 AN: 35194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19377

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54133

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841979

Other (OTH) AF: 0.00 AC: 0 AN: 46068

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.2
DANN	Benign	0.72
PhyloP100		-2.5
PromoterAI		-0.023	Neutral

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

Other links and lift over

dbSNP: rs777882575; hg19: chrX-128873196;