17-68251103-G-T

Variant names:

• chr17-68251103-G-T
• rs782012937
• NM_016627.5:c.511G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016627.5(AMZ2):​c.511G>T​(p.Val171Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,658 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V171M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: AMZ2 NM_016627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.119876236).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016627.5. 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
	AMZ2	NM_016627.5	MANE Select	c.511G>T	p.Val171Leu	missense	Exon 4 of 7	NP_057711.3
	AMZ2	NM_001033569.2		c.511G>T	p.Val171Leu	missense	Exon 5 of 8	NP_001028741.1	Q86W34-4
	AMZ2	NM_001033570.2		c.511G>T	p.Val171Leu	missense	Exon 5 of 8	NP_001028742.1	Q86W34-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMZ2	ENST00000359904.8	TSL:2 MANE Select	c.511G>T	p.Val171Leu	missense	Exon 4 of 7	ENSP00000352976.3	Q86W34-4
	AMZ2	ENST00000392720.6	TSL:1	c.511G>T	p.Val171Leu	missense	Exon 5 of 8	ENSP00000376481.2	Q86W34-4
	AMZ2	ENST00000577985.5	TSL:1	c.511G>T	p.Val171Leu	missense	Exon 3 of 6	ENSP00000464635.1	Q86W34-4

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000399 AC: 10 AN: 250900 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000290

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: 0.00000684 AC: 10 AN: 1461476 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727006

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.000224 AC: 10 AN: 44676

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111900

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

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00216 AC: 33 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000140

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.19
Sift	Benign	0.67	T
Sift4G	Benign	0.13	T
Polyphen		0.96	D
Vest4		0.43
MutPred		0.48		Loss of sheet (P = 0.1501)
MVP		0.50
MPC		0.44
ClinPred		0.16	T
GERP RS		2.5
Varity_R		0.036
gMVP		0.56

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: rs782012937; hg19: chr17-66247244;