17-68250851-A-T

Variant names:

• chr17-68250851-A-T
• rs1599414808
• NM_016627.5:c.341A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016627.5(AMZ2):​c.341A>T​(p.Tyr114Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: AMZ2 NM_016627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40509638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMZ2	NM_016627.5	c.341A>T	p.Tyr114Phe	missense_variant	Exon 3 of 7	ENST00000359904.8	NP_057711.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMZ2	ENST00000359904.8	c.341A>T	p.Tyr114Phe	missense_variant	Exon 3 of 7	2	NM_016627.5	ENSP00000352976.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341A>T (p.Y114F) alteration is located in exon 3 (coding exon 2) of the AMZ2 gene. This alteration results from a A to T substitution at nucleotide position 341, causing the tyrosine (Y) at amino acid position 114 to be replaced by a phenylalanine (F). 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	Benign	0.12
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Benign	0.88
DEOGEN2	Benign	0.019	T;T;T;T;T;.;T;T;T;T;T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	.;D;D;.;.;D;D;D;D;.;.;D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.41	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;.;M;M;M;.;.;.;.;M;M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.99	N;.;.;.;N;.;.;.;.;.;.;.
REVEL	Benign	0.21
Sift	Benign	1.0	T;.;.;.;T;.;.;.;.;.;.;.
Sift4G	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		1.0	D;.;D;D;D;.;.;.;.;D;D;.
Vest4		0.53
MutPred		0.69		Gain of methylation at K116 (P = 0.0696);Gain of methylation at K116 (P = 0.0696);Gain of methylation at K116 (P = 0.0696);Gain of methylation at K116 (P = 0.0696);Gain of methylation at K116 (P = 0.0696);.;Gain of methylation at K116 (P = 0.0696);Gain of methylation at K116 (P = 0.0696);Gain of methylation at K116 (P = 0.0696);Gain of methylation at K116 (P = 0.0696);Gain of methylation at K116 (P = 0.0696);Gain of methylation at K116 (P = 0.0696);
MVP		0.16
MPC		0.14
ClinPred		0.79	D
GERP RS		3.1
Varity_R		0.10
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs1599414808; hg19: chr17-66246992;