7-2700695-G-A

Position:

• chr7-2700695-G-A

Variant summary

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

The NM_001384743.1(AMZ1):​c.244G>A​(p.Ala82Thr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMZ1 NM_001384743.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

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

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=0.068879396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMZ1	NM_001384743.1	c.244G>A	p.Ala82Thr	missense_variant	2/7	ENST00000683327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMZ1	ENST00000683327.1	c.244G>A	p.Ala82Thr	missense_variant	2/7		NM_001384743.1	P1
AMZ1	ENST00000312371.8	c.244G>A	p.Ala82Thr	missense_variant	2/7	1		P1
AMZ1	ENST00000407112.1	c.244G>A	p.Ala82Thr	missense_variant	2/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460666 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2022

The c.244G>A (p.A82T) alteration is located in exon 2 (coding exon 1) of the AMZ1 gene. This alteration results from a G to A substitution at nucleotide position 244, causing the alanine (A) at amino acid position 82 to be replaced by a threonine (T). 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	0.077
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0072	T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.77	N;N
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.99	N;N
REVEL	Benign	0.052
Sift	Benign	0.46	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.69	P;.
Vest4		0.052
MVP		0.099
ClinPred		0.30	T
GERP RS		1.3
Varity_R		0.060
gMVP		0.22

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: rs1215507221; hg19: chr7-2740329; COSMIC: COSV56686077; COSMIC: COSV56686077;