dbSNP rs149467198: AMZ2:p.Leu22Val (chr17-68250251-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016627.5(AMZ2):c.64C>G(p.Leu22Val) variant causes a missense change. The variant allele was found at a frequency of 0.00165 in 1,614,172 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L22F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 2 hom. )

Consequence

AMZ2
NM_016627.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0155905485).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMZ2	NM_016627.5 link	c.64C>G	p.Leu22Val	missense_variant	Exon 2 of 7	ENST00000359904.8	NP_057711.3	Q86W34-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMZ2	ENST00000359904.8 link	c.64C>G	p.Leu22Val	missense_variant	Exon 2 of 7	2	NM_016627.5	ENSP00000352976.3		Q86W34-4

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00119

AC:

299

AN:

251486

Hom.:

AF XY:

0.00111

AC XY:

151

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.00229

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.00172

AC:

2510

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1188

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000899

Gnomad4 NFE exome

AF:

0.00213

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152298

Hom.:

Cov.:

AF XY:

0.000859

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.000914

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00135

AC:

164

EpiCase

AF:

0.00153

EpiControl

AF:

0.00160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Benign

0.92

DEOGEN2

Benign

0.090

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

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

.;D;D;.;.;D;D;D;D;.;.;D

M_CAP

Benign

0.0088

MetaRNN

Benign

0.016

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

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

3.0

M;.;M;M;M;M;.;.;.;M;M;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.1

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

REVEL

Benign

0.098

Sift

Benign

0.072

T;.;.;.;T;D;.;.;.;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;D;D;.;.;.;.;D;D;.

Vest4

0.60

MVP

0.26

MPC

0.48

ClinPred

0.076

GERP RS

3.6

Varity_R

0.26

gMVP

0.57

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over