Variant X-129739220-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003399.6(XPNPEP2):c.7C>T(p.Arg3Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,207,713 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000040 ( 0 hom. 13 hem. )

Consequence

XPNPEP2
NM_003399.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.48

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02745846).

BP6

Variant X-129739220-C-T is Benign according to our data. Variant chrX-129739220-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3191220.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPNPEP2	NM_003399.6 linkuse as main transcript	c.7C>T	p.Arg3Trp	missense_variant	1/21	ENST00000371106.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
XPNPEP2	ENST00000371106.4 linkuse as main transcript	c.7C>T	p.Arg3Trp	missense_variant	1/21	1	NM_003399.6	P1
XPNPEP2	ENST00000371105.7 linkuse as main transcript	n.247C>T		non_coding_transcript_exon_variant	1/6	2
XPNPEP2	ENST00000681234.1 linkuse as main transcript	n.272C>T		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111742

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33896

show subpopulations

Gnomad AFR

AF:

0.0000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000946

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000445

AC:

AN:

179687

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

65427

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000363

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000373

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000401

AC:

AN:

1095971

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

362209

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000166

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000416

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111742

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

33896

show subpopulations

Gnomad4 AFR

AF:

0.0000651

Gnomad4 AMR

AF:

0.0000946

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.1

DANN

Benign

0.97

DEOGEN2

Benign

0.0075

T;T

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-1.4

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.21

Sift

Benign

0.22

T;T

Sift4G

Uncertain

0.035

D;T

Polyphen

0.0

.;B

Vest4

0.11

MutPred

0.33

Loss of disorder (P = 0.0062);Loss of disorder (P = 0.0062);

MVP

0.26

MPC

0.056

ClinPred

0.067

GERP RS

-3.8

Varity_R

0.074

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

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