Variant chrX-129746638-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003399.6(XPNPEP2):c.447T>C(p.Pro149Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,205,591 control chromosomes in the GnomAD database, including 52,644 homozygotes. There are 128,535 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 10119 hom., 12653 hem., cov: 20)

Exomes 𝑓: 0.32 ( 42525 hom. 115882 hem. )

Consequence

XPNPEP2
NM_003399.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.76

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-129746638-T-C is Benign according to our data. Variant chrX-129746638-T-C is described in ClinVar as [Benign]. Clinvar id is 380656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-129746638-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPNPEP2	NM_003399.6 link	c.447T>C	p.Pro149Pro	synonymous_variant	Exon 6 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.447T>C	p.Pro149Pro	synonymous_variant	Exon 6 of 21	1	NM_003399.6	ENSP00000360147.3	O43895
XPNPEP2	ENST00000371105.7 link	n.687T>C		non_coding_transcript_exon_variant	Exon 6 of 6	2
XPNPEP2	ENST00000681234.1 link	n.712T>C		non_coding_transcript_exon_variant	Exon 6 of 7

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

47915

AN:

107644

Hom.:

10114

Cov.:

AF XY:

0.418

AC XY:

12600

AN XY:

30152

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.409

GnomAD3 exomes

AF:

0.384

AC:

70472

AN:

183329

Hom.:

10958

AF XY:

0.370

AC XY:

25056

AN XY:

67767

show subpopulations

Gnomad AFR exome

AF:

0.809

Gnomad AMR exome

AF:

0.363

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.763

Gnomad SAS exome

AF:

0.437

Gnomad FIN exome

AF:

0.294

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.318

AC:

348687

AN:

1097890

Hom.:

42525

Cov.:

AF XY:

0.319

AC XY:

115882

AN XY:

363380

show subpopulations

Gnomad4 AFR exome

AF:

0.814

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.235

Gnomad4 EAS exome

AF:

0.751

Gnomad4 SAS exome

AF:

0.431

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.279

Gnomad4 OTH exome

AF:

0.345

GnomAD4 genome

AF:

0.445

AC:

47973

AN:

107701

Hom.:

10119

Cov.:

AF XY:

0.419

AC XY:

12653

AN XY:

30219

show subpopulations

Gnomad4 AFR

AF:

0.792

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.768

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.316

Hom.:

24673

Bravo

AF:

0.476

EpiCase

AF:

0.266

EpiControl

AF:

0.276

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 15, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.53

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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