17-68250275-A-G

Variant names:

• chr17-68250275-A-G
• rs3213690
• NM_016627.5:c.88A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000359904.8(AMZ2):​c.88A>G​(p.Asn30Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,614,014 control chromosomes in the GnomAD database, including 388,871 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.75 (44212 hom., cov: 32)
  • Exomes 𝑓: 0.68 (344659 hom.)
• Consequence: AMZ2 ENST00000359904.8 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.851
• Publications: 40 publications found

Genes affected

AMZ2 (HGNC:28041): (archaelysin family metallopeptidase 2) The protein encoded by this gene is a zinc metalloprotease that displays some activity against angiotensin-3. The encoded protein is inhibited by the aminopeptidase inhibitor amastatin, as well as by the general inhibitors o-phenanthroline and batimastat. Defects in this gene may be associated with lung tumorigenesis. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.033858E-7).
• BP6: Variant 17-68250275-A-G is Benign according to our data. Variant chr17-68250275-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059188.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359904.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMZ2	NM_016627.5	MANE Select	c.88A>G	p.Asn30Asp	missense	Exon 2 of 7	NP_057711.3
	AMZ2	NM_001033569.2		c.88A>G	p.Asn30Asp	missense	Exon 3 of 8	NP_001028741.1
	AMZ2	NM_001033570.2		c.88A>G	p.Asn30Asp	missense	Exon 3 of 8	NP_001028742.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMZ2	ENST00000359904.8	TSL:2 MANE Select	c.88A>G	p.Asn30Asp	missense	Exon 2 of 7	ENSP00000352976.3
	AMZ2	ENST00000392720.6	TSL:1	c.88A>G	p.Asn30Asp	missense	Exon 3 of 8	ENSP00000376481.2
	AMZ2	ENST00000577985.5	TSL:1	c.88A>G	p.Asn30Asp	missense	Exon 1 of 6	ENSP00000464635.1

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114351 AN: 152012 Hom.: 44140 Cov.: 32

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.741

GnomAD2 exomes AF: 0.718 AC: 180471 AN: 251468 AF XY: 0.709

Gnomad AFR exome AF: 0.935

Gnomad AMR exome AF: 0.841

Gnomad ASJ exome AF: 0.677

Gnomad EAS exome AF: 0.780

Gnomad FIN exome AF: 0.576

Gnomad NFE exome AF: 0.664

Gnomad OTH exome AF: 0.703

GnomAD4 exome AF: 0.684 AC: 999672 AN: 1461880 Hom.: 344659 Cov.: 73 AF XY: 0.684 AC XY: 497400 AN XY: 727242

African (AFR) AF: 0.939 AC: 31435 AN: 33480

American (AMR) AF: 0.834 AC: 37290 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 17868 AN: 26136

East Asian (EAS) AF: 0.742 AC: 29477 AN: 39700

South Asian (SAS) AF: 0.738 AC: 63618 AN: 86258

European-Finnish (FIN) AF: 0.579 AC: 30937 AN: 53416

Middle Eastern (MID) AF: 0.728 AC: 4200 AN: 5766

European-Non Finnish (NFE) AF: 0.668 AC: 742574 AN: 1112004

Other (OTH) AF: 0.700 AC: 42273 AN: 60396

GnomAD4 genome AF: 0.753 AC: 114484 AN: 152134 Hom.: 44212 Cov.: 32 AF XY: 0.751 AC XY: 55833 AN XY: 74356

African (AFR) AF: 0.928 AC: 38526 AN: 41526

American (AMR) AF: 0.793 AC: 12104 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2408 AN: 3470

East Asian (EAS) AF: 0.761 AC: 3940 AN: 5174

South Asian (SAS) AF: 0.749 AC: 3612 AN: 4824

European-Finnish (FIN) AF: 0.577 AC: 6094 AN: 10564

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45416 AN: 67992

Other (OTH) AF: 0.742 AC: 1567 AN: 2112

Alfa AF: 0.698 Hom.: 158821

Bravo AF: 0.777

TwinsUK AF: 0.661 AC: 2452

ALSPAC AF: 0.677 AC: 2608

ESP6500AA AF: 0.925 AC: 4075

ESP6500EA AF: 0.674 AC: 5793

ExAC AF: 0.718 AC: 87162

Asia WGS AF: 0.785 AC: 2729 AN: 3478

EpiCase AF: 0.673

EpiControl AF: 0.674

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	AMZ2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.015	T
MetaRNN	Benign	9.0e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.5	N
PhyloP100		0.85
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.011
MPC		0.10
ClinPred		0.0031	T
GERP RS		1.3
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs3213690; hg19: chr17-66246416; COSMIC: COSV63082480; COSMIC: COSV63082480;