dbSNP rs623980: XPNPEP1: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

new If you want to explore the variant's impact on the transcript NM_020383.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020383.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
XPNPEP1	NM_020383.4	MANE Select	c.653-48T>C	intron	N/A	NP_065116.3
XPNPEP1	NM_001324133.2		c.653-48T>C	intron	N/A	NP_001311062.1
XPNPEP1	NM_001324136.1		c.638-48T>C	intron	N/A	NP_001311065.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XPNPEP1	ENST00000502935.6	TSL:1 MANE Select	c.653-48T>C	intron	N/A	ENSP00000421566.1	Q9NQW7-3
XPNPEP1	ENST00000322238.12	TSL:1	c.653-48T>C	intron	N/A	ENSP00000324011.8	Q9NQW7-4
XPNPEP1	ENST00000488118.6	TSL:1	n.428-48T>C	intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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