7-2702814-C-T

Variant names:

• chr7-2702814-C-T
• rs375783125
• NM_001384743.1:c.397C>T

Variant summary

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

The NM_001384743.1(AMZ1):​c.397C>T​(p.Pro133Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000257 in 1,554,178 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P133L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: AMZ1 NM_001384743.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.96

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMZ1	NM_001384743.1	c.397C>T	p.Pro133Ser	missense_variant	Exon 3 of 7	ENST00000683327.1	NP_001371672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMZ1	ENST00000683327.1	c.397C>T	p.Pro133Ser	missense_variant	Exon 3 of 7		NM_001384743.1	ENSP00000506962.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1401974 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 693196

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: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74360

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.24
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.37		Gain of catalytic residue at P133 (P = 0.0032);Gain of catalytic residue at P133 (P = 0.0032);
MVP		0.37
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.26
gMVP		0.47

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: rs375783125; hg19: chr7-2742448;