7-2700474-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMZ1	NM_001384743.1	c.23A>G	p.Gln8Arg	missense_variant	Exon 2 of 7	ENST00000683327.1	NP_001371672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMZ1	ENST00000683327.1	c.23A>G	p.Gln8Arg	missense_variant	Exon 2 of 7		NM_001384743.1	ENSP00000506962.1
AMZ1	ENST00000312371.8	c.23A>G	p.Gln8Arg	missense_variant	Exon 2 of 7	1		ENSP00000308149.4
AMZ1	ENST00000407112.1	c.23A>G	p.Gln8Arg	missense_variant	Exon 2 of 6	2		ENSP00000386020.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23A>G (p.Q8R) alteration is located in exon 2 (coding exon 1) of the AMZ1 gene. This alteration results from a A to G substitution at nucleotide position 23, causing the glutamine (Q) at amino acid position 8 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.079
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.61	P;.
Vest4		0.48
MutPred		0.28		Gain of solvent accessibility (P = 0.0411);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-2740108;