7-2700646-C-T

Variant names:

• chr7-2700646-C-T
• rs761194583
• NM_001384743.1:c.195C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001384743.1(AMZ1):​c.195C>T​(p.Asp65Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: AMZ1 NM_001384743.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=2.18 with no splicing effect.

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.195C>T	p.Asp65Asp	synonymous	Exon 2 of 7	NP_001371672.1	Q400G9-1
	AMZ1	NM_133463.4		c.195C>T	p.Asp65Asp	synonymous	Exon 2 of 7	NP_597720.1	Q400G9-1
	AMZ1	NM_001384739.1		c.195C>T	p.Asp65Asp	synonymous	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.195C>T	p.Asp65Asp	synonymous	Exon 2 of 7	ENSP00000506962.1	Q400G9-1
	AMZ1	ENST00000312371.8	TSL:1	c.195C>T	p.Asp65Asp	synonymous	Exon 2 of 7	ENSP00000308149.4	Q400G9-1
	AMZ1	ENST00000880040.1		c.195C>T	p.Asp65Asp	synonymous	Exon 2 of 7	ENSP00000550099.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 247032 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459760 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726316

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		2.2

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: rs761194583; hg19: chr7-2740280;