dbSNP rs25651: ANPEP:p.Ser752Asn (chr15-89792557-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001150.3(ANPEP):c.2255G>A(p.Ser752Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,612,620 control chromosomes in the GnomAD database, including 84,996 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 10156 hom., cov: 32)

Exomes 𝑓: 0.32 ( 74840 hom. )

Consequence

ANPEP
NM_001150.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Publications

43 publications found

Variant links:

Genes affected

ANPEP (HGNC:500): (alanyl aminopeptidase, membrane) Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. This membrane-bound zinc metalloprotease is known to serve as a receptor for the HCoV-229E alphacoronavirus as well as other non-human coronaviruses. This gene has also been shown to promote angiogenesis, tumor growth, and metastasis and defects in this gene are associated with various types of leukemia and lymphoma. [provided by RefSeq, Apr 2020]

ANPEP 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 (MetaRNN=3.1119915E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANPEP	NM_001150.3 link	c.2255G>A	p.Ser752Asn	missense_variant	Exon 17 of 21	ENST00000300060.7	NP_001141.2	P15144A0A024RC61Q59E93
ANPEP	NM_001381923.1 link	c.2255G>A	p.Ser752Asn	missense_variant	Exon 17 of 21		NP_001368852.1
ANPEP	NM_001381924.1 link	c.2255G>A	p.Ser752Asn	missense_variant	Exon 16 of 20		NP_001368853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANPEP	ENST00000300060.7 link	c.2255G>A	p.Ser752Asn	missense_variant	Exon 17 of 21	1	NM_001150.3	ENSP00000300060.6		P15144

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53420

AN:

151886

Hom.:

10146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.325

GnomAD2 exomes

AF:

0.301

AC:

75567

AN:

251026

AF XY:

0.302

show subpopulations

Gnomad AFR exome

AF:

0.496

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.240

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.316

AC:

461669

AN:

1460616

Hom.:

74840

Cov.:

AF XY:

0.316

AC XY:

229727

AN XY:

726728

show subpopulations

African (AFR)

AF:

0.502

AC:

16787

AN:

33450

American (AMR)

AF:

0.242

AC:

10806

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

6625

AN:

26120

East Asian (EAS)

AF:

0.227

AC:

9021

AN:

39690

South Asian (SAS)

AF:

0.329

AC:

28394

AN:

86238

European-Finnish (FIN)

AF:

0.216

AC:

11527

AN:

53394

Middle Eastern (MID)

AF:

0.283

AC:

1635

AN:

5768

European-Non Finnish (NFE)

AF:

0.322

AC:

357983

AN:

1110908

Other (OTH)

AF:

0.313

AC:

18891

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

15058

30116

45174

60232

75290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11660

23320

34980

46640

58300

<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:

0.352

AC:

53481

AN:

152004

Hom.:

10156

Cov.:

AF XY:

0.342

AC XY:

25416

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.497

AC:

20608

AN:

41444

American (AMR)

AF:

0.274

AC:

4192

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

881

AN:

3468

East Asian (EAS)

AF:

0.235

AC:

1209

AN:

5154

South Asian (SAS)

AF:

0.340

AC:

1641

AN:

4822

European-Finnish (FIN)

AF:

0.194

AC:

2060

AN:

10598

Middle Eastern (MID)

AF:

0.267

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.318

AC:

21579

AN:

67930

Other (OTH)

AF:

0.325

AC:

688

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1695

3390

5085

6780

8475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.326

Hom.:

37432

Bravo

AF:

0.363

TwinsUK

AF:

0.328

AC:

1218

ALSPAC

AF:

0.329

AC:

1267

ESP6500AA

AF:

0.487

AC:

2142

ESP6500EA

AF:

0.318

AC:

2737

ExAC

AF:

0.309

AC:

37509

Asia WGS

AF:

0.297

AC:

1037

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.010

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.13

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.38

MetaRNN

Benign

0.000031

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.99

PhyloP100

0.094

PrimateAI

Benign

0.29

PROVEAN

Benign

3.0

REVEL

Benign

0.085

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.047

MPC

0.24

ClinPred

0.000023

GERP RS

-4.4

Varity_R

0.055

gMVP

0.35

Mutation Taster

=98/2

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