Variant rs3213690 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_016627.5(AMZ2):c.88A>G(p.Asn30Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,614,014 control chromosomes in the GnomAD database, including 388,871 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.75 ( 44212 hom., cov: 32)

Exomes 𝑓: 0.68 ( 344659 hom. )

Consequence

AMZ2
NM_016627.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.851

Variant links:

Genes affected

AMZ2 (HGNC:28041): (archaelysin family metallopeptidase 2) The protein encoded by this gene is a zinc metalloprotease that displays some activity against angiotensin-3. The encoded protein is inhibited by the aminopeptidase inhibitor amastatin, as well as by the general inhibitors o-phenanthroline and batimastat. Defects in this gene may be associated with lung tumorigenesis. [provided by RefSeq, Oct 2016]

AMZ2 links:

AMZ2 (HGNC:):

AMZ2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.033858E-7).

BP6

Variant 17-68250275-A-G is Benign according to our data. Variant chr17-68250275-A-G is described in ClinVar as [Benign]. Clinvar id is 3059188.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMZ2	NM_016627.5 linkuse as main transcript	c.88A>G	p.Asn30Asp	missense_variant	2/7	ENST00000359904.8	NP_057711.3	Q86W34-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMZ2	ENST00000359904.8 linkuse as main transcript	c.88A>G	p.Asn30Asp	missense_variant	2/7	2	NM_016627.5	ENSP00000352976.3		Q86W34-4

Frequencies

GnomAD3 genomes

AF:

0.752

AC:

114351

AN:

152012

Hom.:

44140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.928

Gnomad AMI

AF:

0.676

Gnomad AMR

AF:

0.792

Gnomad ASJ

AF:

0.694

Gnomad EAS

AF:

0.761

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.741

GnomAD3 exomes

AF:

0.718

AC:

180471

AN:

251468

Hom.:

66043

AF XY:

0.709

AC XY:

96358

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.935

Gnomad AMR exome

AF:

0.841

Gnomad ASJ exome

AF:

0.677

Gnomad EAS exome

AF:

0.780

Gnomad SAS exome

AF:

0.740

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.664

Gnomad OTH exome

AF:

0.703

GnomAD4 exome

AF:

0.684

AC:

999672

AN:

1461880

Hom.:

344659

Cov.:

AF XY:

0.684

AC XY:

497400

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.939

Gnomad4 AMR exome

AF:

0.834

Gnomad4 ASJ exome

AF:

0.684

Gnomad4 EAS exome

AF:

0.742

Gnomad4 SAS exome

AF:

0.738

Gnomad4 FIN exome

AF:

0.579

Gnomad4 NFE exome

AF:

0.668

Gnomad4 OTH exome

AF:

0.700

GnomAD4 genome

AF:

0.753

AC:

114484

AN:

152134

Hom.:

44212

Cov.:

AF XY:

0.751

AC XY:

55833

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.928

Gnomad4 AMR

AF:

0.793

Gnomad4 ASJ

AF:

0.694

Gnomad4 EAS

AF:

0.761

Gnomad4 SAS

AF:

0.749

Gnomad4 FIN

AF:

0.577

Gnomad4 NFE

AF:

0.668

Gnomad4 OTH

AF:

0.742

Alfa

AF:

0.689

Hom.:

79689

Bravo

AF:

0.777

TwinsUK

AF:

0.661

AC:

2452

ALSPAC

AF:

0.677

AC:

2608

ESP6500AA

AF:

0.925

AC:

4075

ESP6500EA

AF:

0.674

AC:

5793

ExAC

AF:

0.718

AC:

87162

Asia WGS

AF:

0.785

AC:

2729

AN:

3478

EpiCase

AF:

0.673

EpiControl

AF:

0.674

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AMZ2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0019

T;T;T;T;T;.;T;T;T;T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.015

.;T;T;.;.;T;T;T;T;.;.;T

MetaRNN

Benign

9.0e-7

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.5

N;.;N;N;N;N;.;.;.;N;N;.

PrimateAI

Benign

0.35

PROVEAN

Benign

1.3

N;.;.;.;N;N;.;.;.;.;.;.

REVEL

Benign

0.027

Sift

Benign

1.0

T;.;.;.;T;T;.;.;.;.;.;.

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;B;B;B;.;.;.;.;B;B;.

Vest4

0.011

MPC

0.10

ClinPred

0.0031

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.13

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over