7-2702742-G-A

Position:

• chr7-2702742-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001384743.1(AMZ1):​c.325G>A​(p.Gly109Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMZ1 NM_001384743.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMZ1	NM_001384743.1	c.325G>A	p.Gly109Arg	missense_variant	3/7	ENST00000683327.1	NP_001371672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMZ1	ENST00000683327.1	c.325G>A	p.Gly109Arg	missense_variant	3/7		NM_001384743.1	ENSP00000506962	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1385628 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.325G>A (p.G109R) alteration is located in exon 3 (coding exon 2) of the AMZ1 gene. This alteration results from a G to A substitution at nucleotide position 325, causing the glycine (G) at amino acid position 109 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	Uncertain	0.34
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.22
Sift	Benign	0.037	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	D;.
Vest4		0.63
MutPred		0.28		Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);
MVP		0.21
ClinPred		0.80	D
GERP RS		4.3
Varity_R		0.21
gMVP		0.58

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: chr7-2742376;