15-89806327-C-T

Position:

chr15-89806327-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein
ANPEP	NM_001150.3 linkuse as main transcript	c.257G>A	p.Arg86Gln	missense_variant	2/21	ENST00000300060.7	NP_001141.2
ANPEP	NM_001381923.1 linkuse as main transcript	c.257G>A	p.Arg86Gln	missense_variant	2/21		NP_001368852.1
ANPEP	NM_001381924.1 linkuse as main transcript	c.257G>A	p.Arg86Gln	missense_variant	1/20		NP_001368853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ANPEP	ENST00000300060.7 linkuse as main transcript	c.257G>A	p.Arg86Gln	missense_variant	2/21	1	NM_001150.3	ENSP00000300060	P1
ANPEP	ENST00000559874.2 linkuse as main transcript	c.257G>A	p.Arg86Gln	missense_variant	2/21	3		ENSP00000452934	P1
ANPEP	ENST00000560137.2 linkuse as main transcript	c.257G>A	p.Arg86Gln	missense_variant	2/21	3		ENSP00000453413	P1
ANPEP	ENST00000679248.1 linkuse as main transcript	c.257G>A	p.Arg86Gln	missense_variant	3/22			ENSP00000502886	P1

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

GnomAD3 exomes

AF:

0.495

AC:

124477

AN:

251446

Hom.:

33058

AF XY:

0.494

AC XY:

67118

AN XY:

135890

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 SAS exome

AF:

0.446

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

Gnomad4 AFR exome

AF:

0.872

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.448

Gnomad4 SAS exome

AF:

0.448

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.533

Gnomad4 OTH exome

AF:

0.535

GnomAD4 genome

AF:

0.595

AC:

90387

AN:

151986

Hom.:

29065

Cov.:

AF XY:

0.583

AC XY:

43339

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.859

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.524

Gnomad4 EAS

AF:

0.462

Gnomad4 SAS

AF:

0.444

Gnomad4 FIN

AF:

0.432

Gnomad4 NFE

AF:

0.526

Gnomad4 OTH

AF:

0.544

Alfa

AF:

0.536

Hom.:

57369

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

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;.

MutationTaster

Benign

1.0

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over