Genetic Variant NM_001384743.1:c.337C>G (chr7-2702754-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001384743.1(AMZ1):c.337C>G(p.Leu113Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L113M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

AMZ1
NM_001384743.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.88

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40835202).

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.337C>G	p.Leu113Val	missense	Exon 3 of 7	NP_001371672.1	Q400G9-1
AMZ1	NM_133463.4		c.337C>G	p.Leu113Val	missense	Exon 3 of 7	NP_597720.1	Q400G9-1
AMZ1	NM_001384739.1		c.337C>G	p.Leu113Val	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.337C>G	p.Leu113Val	missense	Exon 3 of 7	ENSP00000506962.1	Q400G9-1
AMZ1	ENST00000312371.8	TSL:1	c.337C>G	p.Leu113Val	missense	Exon 3 of 7	ENSP00000308149.4	Q400G9-1
AMZ1	ENST00000485540.5	TSL:1	n.457C>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1388692

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31542

American (AMR)

AF:

0.00

AC:

AN:

35776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.00

AC:

AN:

35716

South Asian (SAS)

AF:

0.00

AC:

AN:

79170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4948

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077878

Other (OTH)

AF:

0.0000173

AC:

AN:

57818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0058

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.52

M_CAP

Benign

0.0062

MetaRNN

Benign

0.41

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

1.9

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

REVEL

Benign

0.12

Sift

Benign

0.13

Sift4G

Uncertain

0.014

Polyphen

0.98

Vest4

0.62

MutPred

0.40

Gain of catalytic residue at Q115 (P = 0.0997)

MVP

0.21

ClinPred

0.70

GERP RS

4.3

Varity_R

0.088

gMVP

0.45

Mutation Taster

=87/13

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

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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