chrX-129741825-C-T

Position:

• chrX-129741825-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_003399.6(XPNPEP2):​c.50-283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 111,659 control chromosomes in the GnomAD database, including 1,271 homozygotes. There are 5,277 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (1271 hom., 5277 hem., cov: 23)
• Consequence: XPNPEP2 NM_003399.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.955

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant X-129741825-C-T is Benign according to our data. Variant chrX-129741825-C-T is described in ClinVar as [Benign]. Clinvar id is 1183667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPNPEP2	NM_003399.6	c.50-283C>T		intron_variant		ENST00000371106.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPNPEP2	ENST00000371106.4	c.50-283C>T		intron_variant		1	NM_003399.6	P1
XPNPEP2	ENST00000371105.7	n.290-283C>T		intron_variant, non_coding_transcript_variant		2
XPNPEP2	ENST00000681234.1	n.315-283C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.159 AC: 17696 AN: 111605 Hom.: 1270 Cov.: 23 AF XY: 0.156 AC XY: 5265 AN XY: 33835

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0687

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.0422

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.159 AC: 17702 AN: 111659 Hom.: 1271 Cov.: 23 AF XY: 0.156 AC XY: 5277 AN XY: 33899

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.0939

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.131

Alfa AF: 0.134 Hom.: 940

Bravo AF: 0.165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.69

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: rs5975145; hg19: chrX-128875801;