chr7-2700474-A-G

Variant names:

• chr7-2700474-A-G
• NM_001384743.1:c.23A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384743.1(AMZ1):​c.23A>G​(p.Gln8Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMZ1 NM_001384743.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25753218).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMZ1	NM_001384743.1	MANE Select	c.23A>G	p.Gln8Arg	missense	Exon 2 of 7	NP_001371672.1	Q400G9-1
	AMZ1	NM_133463.4		c.23A>G	p.Gln8Arg	missense	Exon 2 of 7	NP_597720.1	Q400G9-1
	AMZ1	NM_001384739.1		c.23A>G	p.Gln8Arg	missense	Exon 2 of 7	NP_001371668.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMZ1	ENST00000683327.1	MANE Select	c.23A>G	p.Gln8Arg	missense	Exon 2 of 7	ENSP00000506962.1	Q400G9-1
	AMZ1	ENST00000312371.8	TSL:1	c.23A>G	p.Gln8Arg	missense	Exon 2 of 7	ENSP00000308149.4	Q400G9-1
	AMZ1	ENST00000880040.1		c.23A>G	p.Gln8Arg	missense	Exon 2 of 7	ENSP00000550099.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.079
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.61	P
Vest4		0.48
MutPred		0.28		Gain of solvent accessibility (P = 0.0411)
MVP		0.34
ClinPred		0.91	D
GERP RS		4.3
Varity_R		0.16
gMVP		0.66
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr7-2740108;