7-2700508-C-G

Variant names:

• chr7-2700508-C-G
• rs555064289
• NM_001384743.1:c.57C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384743.1(AMZ1):​c.57C>G​(p.Asp19Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D19V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AMZ1 NM_001384743.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031825066).

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.57C>G	p.Asp19Glu	missense	Exon 2 of 7	NP_001371672.1	Q400G9-1
	AMZ1	NM_133463.4		c.57C>G	p.Asp19Glu	missense	Exon 2 of 7	NP_597720.1	Q400G9-1
	AMZ1	NM_001384739.1		c.57C>G	p.Asp19Glu	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.57C>G	p.Asp19Glu	missense	Exon 2 of 7	ENSP00000506962.1	Q400G9-1
	AMZ1	ENST00000312371.8	TSL:1	c.57C>G	p.Asp19Glu	missense	Exon 2 of 7	ENSP00000308149.4	Q400G9-1
	AMZ1	ENST00000880040.1		c.57C>G	p.Asp19Glu	missense	Exon 2 of 7	ENSP00000550099.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454114 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723804

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.0070
DANN	Benign	0.89
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-2.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.062
Sift	Benign	0.38	T
Sift4G	Benign	0.41	T
Polyphen		0.057	B
Vest4		0.13
MutPred		0.20		Gain of ubiquitination at K18 (P = 0.1008)
MVP		0.10
ClinPred		0.42	T
GERP RS		-8.5
Varity_R		0.041
gMVP		0.39
Mutation Taster		=97/3	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

dbSNP: rs555064289; hg19: chr7-2740142;