Variant X-129742138-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003399.6(XPNPEP2):c.80A>C(p.Asp27Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,207,237 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

XPNPEP2
NM_003399.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0270

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPNPEP2	NM_003399.6 link	c.80A>C	p.Asp27Ala	missense_variant	Exon 2 of 21	ENST00000371106.4	NP_003390.4	O43895

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
XPNPEP2	ENST00000371106.4 link	c.80A>C	p.Asp27Ala	missense_variant	Exon 2 of 21	1	NM_003399.6	ENSP00000360147.3	O43895
XPNPEP2	ENST00000371105.7 link	n.320A>C		non_coding_transcript_exon_variant	Exon 2 of 6	2
XPNPEP2	ENST00000681234.1 link	n.345A>C		non_coding_transcript_exon_variant	Exon 2 of 7

Frequencies

GnomAD3 genomes

AF:

0.00000906

AC:

AN:

110398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32682

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000951

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1096839

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362309

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000906

AC:

AN:

110398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32682

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000951

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.80A>C (p.D27A) alteration is located in exon 2 (coding exon 2) of the XPNPEP2 gene. This alteration results from a A to C substitution at nucleotide position 80, causing the aspartic acid (D) at amino acid position 27 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.43

DANN

Benign

0.85

DEOGEN2

Benign

0.0089

T;T

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.58

.;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.33

N;N

REVEL

Benign

0.024

Sift

Benign

0.37

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.013

.;B

Vest4

0.19

MutPred

0.29

Loss of disorder (P = 0.0977);Loss of disorder (P = 0.0977);

MVP

0.061

MPC

0.065

ClinPred

0.052

GERP RS

-1.8

Varity_R

0.062

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.34

Position offset: -30

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