Variant chrX-129742002-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003399.6(XPNPEP2):c.50-106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 712,455 control chromosomes in the GnomAD database, including 10,794 homozygotes. There are 32,243 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 3852 hom., 7590 hem., cov: 22)

Exomes 𝑓: 0.15 ( 6942 hom. 24653 hem. )

Consequence

XPNPEP2
NM_003399.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.131

Variant links:

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]

XPNPEP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-129742002-G-A is Benign according to our data. Variant chrX-129742002-G-A is described in ClinVar as [Benign]. Clinvar id is 1252667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPNPEP2	NM_003399.6 linkuse as main transcript	c.50-106G>A		intron_variant		ENST00000371106.4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
XPNPEP2	ENST00000371106.4 linkuse as main transcript	c.50-106G>A	intron_variant	1	NM_003399.6	P1
XPNPEP2	ENST00000371105.7 linkuse as main transcript	n.290-106G>A	intron_variant, non_coding_transcript_variant	2
XPNPEP2	ENST00000681234.1 linkuse as main transcript	n.315-106G>A	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

26558

AN:

111254

Hom.:

3852

Cov.:

AF XY:

0.226

AC XY:

7563

AN XY:

33508

show subpopulations

Gnomad AFR

AF:

0.529

Gnomad AMI

AF:

0.0667

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.0746

Gnomad MID

AF:

0.0591

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.146

AC:

87485

AN:

601148

Hom.:

6942

AF XY:

0.156

AC XY:

24653

AN XY:

157808

show subpopulations

Gnomad4 AFR exome

AF:

0.547

Gnomad4 AMR exome

AF:

0.0894

Gnomad4 ASJ exome

AF:

0.0555

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.0841

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.239

AC:

26588

AN:

111307

Hom.:

3852

Cov.:

AF XY:

0.226

AC XY:

7590

AN XY:

33571

show subpopulations

Gnomad4 AFR

AF:

0.529

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.454

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.0746

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.139

Hom.:

5567

Bravo

AF:

0.258

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.82

CADD

Benign

1.0

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over