7-2709063-ATC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001384743.1(AMZ1):c.602-5_602-4del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,564,346 control chromosomes in the GnomAD database, including 77 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (48 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (29 hom.)
• Consequence: AMZ1 NM_001384743.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0440

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 7-2709063-ATC-A is Benign according to our data. Variant chr7-2709063-ATC-A is described in ClinVar as [Benign]. Clinvar id is 781022.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1725/152240) while in subpopulation AFR AF= 0.0394 (1638/41528). AF 95% confidence interval is 0.0379. There are 48 homozygotes in gnomad4. There are 814 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMZ1	NM_001384743.1	c.602-5_602-4del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000683327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMZ1	ENST00000683327.1	c.602-5_602-4del		splice_polypyrimidine_tract_variant, intron_variant			NM_001384743.1	P1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1723 AN: 152122 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00283 AC: 596 AN: 210774 Hom.: 11 AF XY: 0.00224 AC XY: 256 AN XY: 114534

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000433

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000102

Gnomad OTH exome AF: 0.000594

GnomAD4 exome AF: 0.00105 AC: 1482 AN: 1412106 Hom.: 29 AF XY: 0.000964 AC XY: 673 AN XY: 698178

Gnomad4 AFR exome AF: 0.0410

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000254

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000202

Gnomad4 OTH exome AF: 0.00186

GnomAD4 genome AF: 0.0113 AC: 1725 AN: 152240 Hom.: 48 Cov.: 33 AF XY: 0.0109 AC XY: 814 AN XY: 74434

Gnomad4 AFR AF: 0.0394

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00582 Hom.: 3

Bravo AF: 0.0125

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs144574079; hg19: chr7-2748697;