Genetic Variant NM_020383.4:c.653-48T>C (chr10-109886389-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020383.4(XPNPEP1):c.653-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,574,810 control chromosomes in the GnomAD database, including 251,906 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 19736 hom., cov: 33)

Exomes 𝑓: 0.56 ( 232170 hom. )

Consequence

XPNPEP1
NM_020383.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

13 publications found

Variant links:

Genes affected

XPNPEP1 (HGNC:12822): (X-prolyl aminopeptidase 1) This gene encodes the cytosolic form of a metalloaminopeptidase that catalyzes the cleavage of the N-terminal amino acid adjacent to a proline residue. The gene product may play a role in degradation and maturation of tachykinins, neuropeptides, and peptide hormones. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Nov 2009]

XPNPEP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPNPEP1	NM_020383.4 link	c.653-48T>C		intron_variant	Intron 7 of 20	ENST00000502935.6	NP_065116.3	Q9NQW7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPNPEP1	ENST00000502935.6 link	c.653-48T>C		intron_variant	Intron 7 of 20	1	NM_020383.4	ENSP00000421566.1		Q9NQW7-3

Frequencies

GnomAD3 genomes

AF:

0.496

AC:

75382

AN:

151986

Hom.:

19734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.728

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.266

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.489

GnomAD2 exomes

AF:

0.478

AC:

108144

AN:

226460

AF XY:

0.478

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.325

Gnomad ASJ exome

AF:

0.561

Gnomad EAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.561

Gnomad NFE exome

AF:

0.597

Gnomad OTH exome

AF:

0.523

GnomAD4 exome

AF:

0.561

AC:

798578

AN:

1422706

Hom.:

232170

Cov.:

AF XY:

0.555

AC XY:

392798

AN XY:

708196

show subpopulations

African (AFR)

AF:

0.384

AC:

12494

AN:

32518

American (AMR)

AF:

0.334

AC:

14197

AN:

42568

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

14512

AN:

25674

East Asian (EAS)

AF:

0.278

AC:

10793

AN:

38822

South Asian (SAS)

AF:

0.306

AC:

25656

AN:

83780

European-Finnish (FIN)

AF:

0.569

AC:

29941

AN:

52630

Middle Eastern (MID)

AF:

0.451

AC:

2568

AN:

5692

European-Non Finnish (NFE)

AF:

0.607

AC:

657129

AN:

1081928

Other (OTH)

AF:

0.529

AC:

31288

AN:

59094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

16634

33268

49902

66536

83170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17440

34880

52320

69760

87200

<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:

0.496

AC:

75398

AN:

152104

Hom.:

19736

Cov.:

AF XY:

0.487

AC XY:

36203

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.387

AC:

16061

AN:

41492

American (AMR)

AF:

0.405

AC:

6199

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1936

AN:

3470

East Asian (EAS)

AF:

0.266

AC:

1374

AN:

5164

South Asian (SAS)

AF:

0.291

AC:

1405

AN:

4828

European-Finnish (FIN)

AF:

0.551

AC:

5824

AN:

10574

Middle Eastern (MID)

AF:

0.486

AC:

142

AN:

292

European-Non Finnish (NFE)

AF:

0.600

AC:

40774

AN:

67972

Other (OTH)

AF:

0.483

AC:

1019

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1922

3844

5766

7688

9610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.552

Hom.:

20504

Bravo

AF:

0.483

Asia WGS

AF:

0.251

AC:

877

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.86

(source)

DANN

Benign

0.67

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over