dbSNP rs2273740: XPNPEP1:c.1242-10T>G (chr10-109877877-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_020383.4(XPNPEP1):c.1242-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,996 control chromosomes in the GnomAD database, including 31,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.20 ( 3644 hom., cov: 33)

Exomes 𝑓: 0.18 ( 27998 hom. )

Consequence

XPNPEP1
NM_020383.4 intron

Scores

Splicing: ADA: 0.03768

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.47

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 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.1242-10T>G	intron	N/A	NP_065116.3
XPNPEP1	NM_001324133.2		c.1242-10T>G	intron	N/A	NP_001311062.1
XPNPEP1	NM_001324136.1		c.1227-10T>G	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.1242-10T>G	intron	N/A	ENSP00000421566.1	Q9NQW7-3
XPNPEP1	ENST00000322238.12	TSL:1	c.1242-10T>G	intron	N/A	ENSP00000324011.8	Q9NQW7-4
XPNPEP1	ENST00000488118.6	TSL:1	n.1017-10T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30889

AN:

152060

Hom.:

3637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.216

AC:

54362

AN:

251432

AF XY:

0.228

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.0827

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.179

AC:

261196

AN:

1461816

Hom.:

27998

Cov.:

AF XY:

0.186

AC XY:

135507

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.236

AC:

7902

AN:

33480

American (AMR)

AF:

0.0882

AC:

3943

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

4722

AN:

26136

East Asian (EAS)

AF:

0.320

AC:

12685

AN:

39700

South Asian (SAS)

AF:

0.425

AC:

36644

AN:

86254

European-Finnish (FIN)

AF:

0.283

AC:

15100

AN:

53420

Middle Eastern (MID)

AF:

0.225

AC:

1297

AN:

5764

European-Non Finnish (NFE)

AF:

0.150

AC:

167059

AN:

1111948

Other (OTH)

AF:

0.196

AC:

11844

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

11725

23450

35174

46899

58624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6144

12288

18432

24576

30720

<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:

0.203

AC:

30919

AN:

152180

Hom.:

3644

Cov.:

AF XY:

0.214

AC XY:

15896

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.235

AC:

9774

AN:

41520

American (AMR)

AF:

0.130

AC:

1986

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

634

AN:

3470

East Asian (EAS)

AF:

0.352

AC:

1820

AN:

5168

South Asian (SAS)

AF:

0.429

AC:

2068

AN:

4824

European-Finnish (FIN)

AF:

0.308

AC:

3259

AN:

10582

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10839

AN:

67992

Other (OTH)

AF:

0.181

AC:

383

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1222

2443

3665

4886

6108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.180

Hom.:

873

Bravo

AF:

0.185

Asia WGS

AF:

0.388

AC:

1349

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.038

dbscSNV1_RF

Benign

0.28

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over