17-68250273-T-C

Variant names:

• chr17-68250273-T-C
• NM_016627.5:c.86T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016627.5(AMZ2):​c.86T>C​(p.Leu29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMZ2 NM_016627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0959115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMZ2	NM_016627.5	c.86T>C	p.Leu29Ser	missense_variant	Exon 2 of 7	ENST00000359904.8	NP_057711.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMZ2	ENST00000359904.8	c.86T>C	p.Leu29Ser	missense_variant	Exon 2 of 7	2	NM_016627.5	ENSP00000352976.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.86T>C (p.L29S) alteration is located in exon 2 (coding exon 1) of the AMZ2 gene. This alteration results from a T to C substitution at nucleotide position 86, causing the leucine (L) at amino acid position 29 to be replaced by a serine (S). 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	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Benign	0.88
DEOGEN2	Benign	0.050	T;T;T;T;T;.;T;T;T;T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.57	.;T;T;.;.;T;T;T;T;.;.;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.096	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.;M;M;M;M;.;.;.;M;M;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;.;.;.;N;N;.;.;.;.;.;.
REVEL	Benign	0.060
Sift	Uncertain	0.028	D;.;.;.;D;D;.;.;.;.;.;.
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.90	P;.;P;P;P;.;.;.;.;P;P;.
Vest4		0.39
MutPred		0.35		Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP		0.43
MPC		0.42
ClinPred		0.72	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-66246414;