dbSNP rs774159719: XPNPEP2:p.Asp114Asn (chrX-129746277-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003399.6(XPNPEP2):c.340G>A(p.Asp114Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,209,812 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.000032 ( 0 hom. 12 hem. )

Consequence

XPNPEP2
NM_003399.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.86

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

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.340G>A	p.Asp114Asn	missense	Exon 5 of 21	NP_003390.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XPNPEP2	ENST00000371106.4	TSL:1 MANE Select	c.340G>A	p.Asp114Asn	missense	Exon 5 of 21	ENSP00000360147.3	O43895
XPNPEP2	ENST00000880532.1		c.388G>A	p.Asp130Asn	missense	Exon 5 of 21	ENSP00000550591.1
XPNPEP2	ENST00000880530.1		c.340G>A	p.Asp114Asn	missense	Exon 5 of 21	ENSP00000550589.1

Frequencies

GnomAD3 genomes

AF:

0.0000624

AC:

AN:

112233

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000839

Gnomad SAS

AF:

0.00111

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000659

AC:

AN:

182226

AF XY:

0.0000449

show subpopulations

Gnomad AFR exome

AF:

0.0000763

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000722

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000319

AC:

AN:

1097527

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

362989

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26393

American (AMR)

AF:

0.00

AC:

AN:

35193

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19380

East Asian (EAS)

AF:

0.000497

AC:

AN:

30202

South Asian (SAS)

AF:

0.0000555

AC:

AN:

54076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40238

Middle Eastern (MID)

AF:

0.000251

AC:

AN:

3977

European-Non Finnish (NFE)

AF:

0.0000178

AC:

AN:

842010

Other (OTH)

AF:

0.0000217

AC:

AN:

46058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000623

AC:

AN:

112285

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

34449

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30957

American (AMR)

AF:

0.00

AC:

AN:

10617

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.000842

AC:

AN:

3565

South Asian (SAS)

AF:

0.00111

AC:

AN:

2691

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6109

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53253

Other (OTH)

AF:

0.00

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000659

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.66

MetaRNN

Uncertain

0.66

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

4.5

PhyloP100

6.9

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.0

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.36

MutPred

0.87

Gain of MoRF binding (P = 0.0479)

MVP

0.57

MPC

0.35

ClinPred

0.96

GERP RS

5.4

Varity_R

0.79

gMVP

0.96

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over