15-89806327-C-T

Variant names:

Variant summary

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

The NM_001150.3(ANPEP):c.257G>A(p.Arg86Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,613,860 control chromosomes in the GnomAD database, including 233,638 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 0.59 ( 29065 hom., cov: 32)

Exomes 𝑓: 0.52 ( 204573 hom. )

Consequence

ANPEP
NM_001150.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.409

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=5.6368644E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ANPEP	NM_001150.3 link	c.257G>A	p.Arg86Gln	missense_variant	Exon 2 of 21	ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1 link	c.257G>A	p.Arg86Gln	missense_variant	Exon 2 of 21		NP_001368852.1
ANPEP	NM_001381924.1 link	c.257G>A	p.Arg86Gln	missense_variant	Exon 1 of 20		NP_001368853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ANPEP	ENST00000300060.7 link	c.257G>A	p.Arg86Gln	missense_variant	Exon 2 of 21	1	NM_001150.3	ENSP00000300060.6
ANPEP	ENST00000559874.2 link	c.257G>A	p.Arg86Gln	missense_variant	Exon 2 of 21	3		ENSP00000452934.2
ANPEP	ENST00000560137.2 link	c.257G>A	p.Arg86Gln	missense_variant	Exon 2 of 21	3		ENSP00000453413.2
ANPEP	ENST00000679248.1 link	c.257G>A	p.Arg86Gln	missense_variant	Exon 3 of 22			ENSP00000502886.1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90295

AN:

151868

Hom.:

29013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.859

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.544

GnomAD2 exomes

AF:

0.495

AC:

124477

AN:

251446

AF XY:

0.494

show subpopulations

Gnomad AFR exome

AF:

0.864

Gnomad AMR exome

AF:

0.307

Gnomad ASJ exome

AF:

0.522

Gnomad EAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.433

Gnomad NFE exome

AF:

0.527

Gnomad OTH exome

AF:

0.494

GnomAD4 exome

AF:

0.524

AC:

765668

AN:

1461874

Hom.:

204573

Cov.:

AF XY:

0.521

AC XY:

379248

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.872

AC:

29185

AN:

33480

American (AMR)

AF:

0.320

AC:

14299

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

13729

AN:

26136

East Asian (EAS)

AF:

0.448

AC:

17766

AN:

39700

South Asian (SAS)

AF:

0.448

AC:

38684

AN:

86258

European-Finnish (FIN)

AF:

0.440

AC:

23506

AN:

53416

Middle Eastern (MID)

AF:

0.526

AC:

3034

AN:

5768

European-Non Finnish (NFE)

AF:

0.533

AC:

593147

AN:

1111996

Other (OTH)

AF:

0.535

AC:

32318

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

25787

51574

77361

103148

128935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16948

33896

50844

67792

84740

<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:

0.595

AC:

90387

AN:

151986

Hom.:

29065

Cov.:

AF XY:

0.583

AC XY:

43339

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.859

AC:

35640

AN:

41472

American (AMR)

AF:

0.423

AC:

6445

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1820

AN:

3472

East Asian (EAS)

AF:

0.462

AC:

2382

AN:

5156

South Asian (SAS)

AF:

0.444

AC:

2135

AN:

4812

European-Finnish (FIN)

AF:

0.432

AC:

4571

AN:

10576

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.526

AC:

35730

AN:

67940

Other (OTH)

AF:

0.544

AC:

1149

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1718

3436

5155

6873

8591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.543

Hom.:

107683

Bravo

AF:

0.608

TwinsUK

AF:

0.542

AC:

2011

ALSPAC

AF:

0.538

AC:

2074

ESP6500AA

AF:

0.847

AC:

3726

ESP6500EA

AF:

0.525

AC:

4515

ExAC

AF:

0.510

AC:

61877

Asia WGS

AF:

0.474

AC:

1649

AN:

3478

EpiCase

AF:

0.526

EpiControl

AF:

0.520

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.10

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.087

T;T

MetaRNN

Benign

0.0000056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.12

N;.

PhyloP100

-0.41

PrimateAI

Benign

0.20

PROVEAN

Benign

0.70

N;N

REVEL

Benign

0.014

Sift

Benign

0.66

T;T

Sift4G

Benign

0.53

T;.

Polyphen

0.0

B;.

Vest4

0.020

MPC

0.29

ClinPred

0.0019

GERP RS

-5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.098

gMVP

0.41

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over