Genetic Variant AMZ1:p.Pro133Arg (chr7-2702815-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001384743.1(AMZ1):c.398C>G(p.Pro133Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000356 in 1,402,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P133T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

AMZ1
NM_001384743.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.96

Publications

0 publications found

Variant links:

Genes affected

AMZ1 (HGNC:22231): (archaelysin family metallopeptidase 1) Predicted to enable metal ion binding activity and metallopeptidase activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

AMZ1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.767

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384743.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMZ1	NM_001384743.1	MANE Select	c.398C>G	p.Pro133Arg	missense	Exon 3 of 7	NP_001371672.1	Q400G9-1
AMZ1	NM_133463.4		c.398C>G	p.Pro133Arg	missense	Exon 3 of 7	NP_597720.1	Q400G9-1
AMZ1	NM_001384739.1		c.398C>G	p.Pro133Arg	missense	Exon 3 of 7	NP_001371668.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMZ1	ENST00000683327.1	MANE Select	c.398C>G	p.Pro133Arg	missense	Exon 3 of 7	ENSP00000506962.1	Q400G9-1
AMZ1	ENST00000312371.8	TSL:1	c.398C>G	p.Pro133Arg	missense	Exon 3 of 7	ENSP00000308149.4	Q400G9-1
AMZ1	ENST00000485540.5	TSL:1	n.518C>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000122

AC:

AN:

163402

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000293

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1402942

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

693760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32018

American (AMR)

AF:

0.00

AC:

AN:

37926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25262

East Asian (EAS)

AF:

0.00

AC:

AN:

36428

South Asian (SAS)

AF:

0.00

AC:

AN:

79844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41230

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.00000368

AC:

AN:

1086252

Other (OTH)

AF:

0.0000171

AC:

AN:

58350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000224

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

PhyloP100

6.0

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.28

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.89

MutPred

0.41

Gain of MoRF binding (P = 0.0036)

MVP

0.33

ClinPred

0.99

GERP RS

5.2

Varity_R

0.39

gMVP

0.45

Mutation Taster

=82/18

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over